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Kako se virus lijepi na nebiološku površinu?

Kako se virus lijepi na nebiološku površinu?



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Nedavni događaji pobudili su ponovno zanimanje za razumijevanje načina na koji virus može ostati na površini.

Radi argumenta, pretpostavimo da imamo posla s virusom tipa Corona. Zatim se može nagađati da se virus lijepi za (neorgansku) površinu zbog interakcije London-Force (Van der Waalsove sile) između površine i virusa Spike S protein. Ali stvarno nemam pojma i to je samo divlja pretpostavka.

Tražim istraživanja i eksperimente na ovu temu, ali ih ne mogu pronaći, najvjerojatnije zato što ne postavljam Googleu pravo pitanje niti koristim ispravan jezik biologije.

Kako virus ostaje vezan za nebiološku površinu?
(Postoje li za to mjere "ljepljivosti"?)

P.S. Kada kažem nebiološki, Mislim staklo, metal i plastika.


7.7: Karakteristike virusa

  • Doprinos CK-12: Biološki koncepti
  • Izvor iz Zaklade CK-12

Ovaj virus izgleda živo, ali je li tako?

Primijetite veliki virus. On (ili ona) izgleda jako ljutito. Ali zapravo virusi ne mogu biti ni "quothe & quot" ni "quothe & quot" - niti veliki. Zapravo, virusi su najmanje stvari. Mnogo manji od većine prokariota. Također ne možemo reći da su virusi najmanja živa bića ili organizmi, jer virusi ne zadovoljavaju definiciju živog ili organizma.


Zašto se bakterije tako dobro lijepe za plastične površine?

Joanna Verran - Ako nemate ništa protiv, morat ću se vratiti unatrag i općenito govoriti o bugovima na površinama.

Bakterije općenito na planetu žive pričvršćene na površine. Većina ih je pričvršćena na površine pa bi upravo tamo najradije bili. Ako ste imali bakterije u ustima, ako ih progutate, one umiru, ali ako vam se lijepe za zube, to im je puno bolje. To je najbolje mjesto za pričvršćivanje na površinu. Zalijepit će se za mnogo različitih površina.

U prehrambenoj industriji i gdje smo govorili o površinama u bolnicama samo gledate na preživljavanje organizama koji su se zalijepili na površinu. Možda su ih tamo stavili ljudi koji su ih dodirnuli ili su daskom za rezanje došli u dodir s površinom kroz meso ili bilo što što je usitnjeno. To je neka vrsta kontakta i preživljavanja. Organizmi se nisu vezali. Tek su tamo stavljeni i onda preživljavaju. Taj prilog nazivamo sučeljem s čvrstim zrakom.

Ako dopustite organizmima da rastu na površini koja ima tekućinu na sučelju čvrste tekućine, to nazivamo biofilmom. Opet, iako organizmi to vrlo rado čine, zalijepit će se za površinu i zatim rasti. Na kružni način oni će se držati bilo čega doista i pokušava im smanjiti sposobnost lijepljenja.

Druga stvar s biofilmovima - ako razmišljate o kateterima ili kontaktnim lećama ili protezama - bilo kakvoj plastici koju biste mogli implantirati u tijelo. Prva stvar koja će se zalijepiti za te materijale su organske molekule iz tekućine oko njih. To može biti slina ili suzna tekućina ili proteini u mokraći. Tada će se bakterije zalijepiti za njih. Biofilm će se također formirati na vrhu te uvjetovane površine.


Istraživači stvaraju vrhunski neprianjajući premaz koji odbija sve-čak i viruse i bakterije

Tim istraživača sa Sveučilišta McMaster razvio je površinu za samočišćenje koja može odbiti sve oblike bakterija, sprječavajući prijenos bakterija otpornih na antibiotike i drugih opasnih bakterija u okruženjima, od bolnica do kuhinja.

Nova plastična površina-tretirani oblik konvencionalnog prozirnog omota-može se skupljati na kvakama vrata, ogradama, IV postoljima i drugim površinama koje mogu biti magneti za bakterije poput MRSA i C. difficile.

Obrađeni materijal idealan je i za pakiranje hrane, gdje bi mogao zaustaviti slučajni prijenos bakterija poput E coli, Salmonela i listerije iz sirove piletine, mesa i druge hrane, kako je opisano u radu objavljenom 13. prosinca 2019. u časopisu ACS Nano.

Istraživanje su vodili inženjeri Leyla Soleymani i Tohid Didar, koji su surađivali s kolegama s McMaster ’s Instituta za istraživanje zaraznih bolesti i Kanadskog centra za elektronsku mikroskopiju sa sjedištem u McMasteru.

Nova folija koju su razvili istraživači sa Sveučilišta McMaster odbija sve što dođe u dodir s njom, uključujući viruse i bakterije. Zasluge: Georgia Kirkos, Sveučilište McMaster

Nadahnuta vodootpornim lotosovim listom, nova površina funkcionira kombinacijom nanorazličitog površinskog inženjeringa i kemije. Površina je teksturirana mikroskopskim borama koje isključuju sve vanjske molekule. Na primjer, kap vode ili krvi jednostavno odskoči kad padne na površinu. Isto vrijedi i za bakterije.

"Mi strukturno prilagođavamo tu plastiku", kaže Soleymani, inženjerski fizičar. “Ovaj materijal daje nam nešto što se može primijeniti na sve vrste stvari. ”

Površina se također kemijski obrađuje kako bi se dodatno poboljšala njezina odbojna svojstva, što rezultira fleksibilnom, izdržljivom i jeftinom reprodukcijom barijere.

Tim istraživača McMastera Leyla Soleymani razvio je novu plastičnu površinu koja odbija sve oblike bakterija i virusa. Zasluge: Georgia Kirkos, Sveučilište McMaster

“Vidimo da se ova tehnologija koristi u svim vrstama institucionalnih i domaćih okruženja ", kaže Didar. “Dok se svijet suočava s krizom otpornosti na mikrobe, nadamo se da će postati važan dio antibakterijskog alata. ”

Znanstvenici su testirali materijal pomoću dva najneugodnija oblika bakterija otpornih na antibiotike: MRSA i Pseudomonas, u suradnji s Ericom Brownom iz McMaster & Instituta za istraživanje zaraznih bolesti.

Istraživač McMastera Tohid Didar bio je dio tima koji je razvio novu plastičnu površinu koja odbija sve bakterije i viruse. Zasluge: Georgia Kirkos, Sveučilište McMaster

Inženjerka Kathryn Grandfield pomogla je timu provjeriti učinkovitost površine snimanjem snimaka elektronskim mikroskopom koji pokazuju da se praktički nijedna bakterija ne može prenijeti na novu površinu.

Istraživači se nadaju suradnji s komercijalnim partnerom na razvoju komercijalnih aplikacija za omote.

Referenca: “Fleksibilni hijerarhijski omoti odbijaju gram-negativne i pozitivne bakterije otporne na lijekove ” by Sara M. Imani, Roderick Maclachlan, Kenneth Rachwalski, Yuting Chan, Bryan Lee, Mark McInnes, Kathryn Grandfield, Eric D. Brown, Tohid F Didar i Leyla Soleymani, 13. prosinca 2019., ACS Nano.
DOI: 10.1021/acsnano.9b06287

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6 komentara na "Istraživači stvaraju vrhunski neprianjajući premaz koji odbija sve-čak i viruse i bakterije"

Što Kanađani najčešće dodiruju kao uobičajene kontaktne točke i rijetko su, ako ikad dezinficirani? Mlaznice za benzinske pumpe, slušalice za javne telefone, kolica za kupnju, ručke na vratima trgovačkih centara, rukohvati za javni prijevoz u autobusima, vlakovima, stanicama, rukohvati za pokretne stepenice, lopatice za rasuti teret, bankomati, bankovni strojevi i tipkovnice i dodirne pločice na prodajnim mjestima. Što gotovo svakodnevno dodirujete što gotovo svi drugi dodiruju?

Dugoročna svemirska putovanja i interijeri svemirskih stanica bit će prepuni bakterija, virusa i superbakterija.

Ovo je u javnom interesu i interesu svjetskog zdravlja. Ne može i ne smije pasti u ruke i kategoriju intelektualnog vlasništva. Pripada čovječanstvu.

Bilo je krajnje vrijeme da se riješi ovaj problem, …. Pitam se je li ovo izneseno u spremniku morskih pasa lol, … bi li dobili 5 morskih pasa koji se bore za dogovor. Vidim nekoliko tvrtki koje se nadaju da neće doći na tržište jer bi proizvodi koje proizvode završili zastarjeli. ..ali to je znak vremena i sjajni istraživački timovi poput ovih spomenutih … .. sad tip koji ima pacijenta za zauvijek žarulju? ? …. ili ljudi koji imaju sjajne ideje?, ….da tvrtke NE ŽELE izlaziti na tržište jer će ostati bez posla? , Givin mora imati priliku pokazati svijetu što je njihov talent
Ovaj komentar je samo o ovom članku i vidim velike mogućnosti koje će ovo otkriće učiniti da promijeni svijet. … nadam se da ljudi koji su zaduženi za njegovu prodaju ili distribuciju nisu osvojili cijenu tamo gdje je nedostupna. ….ya ya … kažu da će biti izdržljiv i jeftin. …, ali ako su jedini koji imaju pacijenta da to učini … .. onda je to otvoreno za nekoga tko ga monopolizira radi financijske dobiti
Drugi komentar kaže da je to za čovječanstvo. …..Slažem se, … neka se nadaju da tvrtka koja ga proizvodi, ne drži čovječanstvo kao taoce, pohlepom

I naravno, orat će naprijed i staviti ovaj materijal na sve prije nego razmisle o tome ispire li opasne kemikalije u hranu i okoliš, gdje će završiti u ljudima.

U svom iskustvu čistačice otkrio sam da je čisto malo ako bilo koja komercijalna vrijednost kao sanitacija ne doprinosi dobiti, barem ne izravno. NITKO nije spreman platiti sanitaciju, pa kako će ovaj proizvod doći do javnih mjesta. Točka I slučaja: upravitelji bolnica u središnjoj zemlji ne misle da radni autoklav nije nužan za bolničke operacije. Skupina kirurga trebala je niz pritužbi u pokrajinu kako bi zatvorila operaciju dok se autoklav ne popravi. Operacije su se čuvale mjesecima. Pogodite kolika je bila vrijednost paketa za otpuštanje administratora#8217. Većina nas ne bi vidjela toliko novca da imamo dobitak na loto jackpotu.

Dobro je znati da virus i bakterije neće ostati na premazu. Međutim, virus i bakterija će sletjeti na neka druga mjesta. Bolje je samo ih ubiti na mjestu s premazom i naznačiti nakupljanje virusa kada količina pređe siguran prag i ljudi ih na kraju mogu očistiti.

Ovaj premaz koji se ne lijepi vrlo je koristan u ovo doba pandemije. Cijeli svijet pati od smrtonosnog virusa COVID-19 i ova vrsta istraživanja može pomoći čovječanstvu da se spasi i izliječi. Osim ovoga, predlažem da svi isprobaju najbolje aplikacije za vježbanje za Android kako bi ostali zdravi u 2020.

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Znanstvenici koji koriste računalno modeliranje za proučavanje SARS-CoV-2, virusa koji je izazvao pandemiju COVID-19, otkrili su da je virus najidealnije prilagođen za inficiranje ljudi …


Ono što koronavirus čini vašem tijelu čini ga tako smrtonosnim

Biologija virusa pomoći će nam da naučimo kako se boriti protiv njega.

COVID-19 uzrokuje koronavirus nazvan SARS-CoV-2. Koronavirusi pripadaju skupini virusa koji inficiraju životinje, od paunova do kitova. Nazvani su po šiljcima s vrhovima žarulja koji strše s površine virusa i daju izgled korone koja ga okružuje.

Infekcija koronavirusom obično se odvija na jedan od dva načina: kao infekcija u plućima koja uključuje neke slučajeve onoga što bi ljudi nazvali prehlada, ili kao infekcija u crijevima koja uzrokuje proljev. COVID-19 počinje u plućima poput koronavirusa prehlade, ali zatim izaziva haos u imunološkom sustavu koji može dovesti do dugotrajnog oštećenja pluća ili smrti.

SARS-CoV-2 genetski je vrlo sličan drugim ljudskim respiratornim koronavirusima, uključujući SARS-CoV i MERS-CoV. Međutim, suptilne genetske razlike dovode do značajnih razlika u tome koliko lako koronavirus zarazi ljude i kako se od njih razboli.

SARS-CoV-2 ima svu istu genetsku opremu kao i izvorni SARS-CoV, koji je 2003. izazvao globalnu epidemiju, ali s oko 6.000 mutacija posutih na uobičajena mjesta gdje se mijenjaju koronavirusi. Razmislite o punomasnom mlijeku u odnosu na obrano mlijeko.

U usporedbi s drugim ljudskim koronavirusima poput MERS-CoV-a, koji se pojavio na Bliskom istoku 2012. godine, novi virus ima prilagođene verzije iste opće opreme za invaziju stanica i samo kopiranje. Međutim, SARS-CoV-2 ima potpuno drugačiji skup gena koji se nazivaju dodaci, koji ovom novom virusu daju malu prednost u specifičnim situacijama. Na primjer, MERS ima određeni protein koji isključuje sposobnost stanice da oglasi alarm zbog virusnog uljeza. SARS-CoV-2 ima nepovezan gen sa zasad nepoznatom funkcijom u tom položaju u svom genomu. Razmislite o kravljem mlijeku u odnosu na bademovo mlijeko.

Kako se virus inficira

Svaka infekcija koronavirusom počinje česticom virusa, sfernom ljuskom koja štiti jedan dugi niz genetskog materijala i ubacuje ga u ljudsku stanicu. Genetski materijal upućuje stanicu da napravi oko 30 različitih dijelova virusa, dopuštajući virusu da se razmnožava. Stanice koje SARS-CoV-2 radije zarazi imaju izvana protein nazvan ACE2 koji je važan za regulaciju krvnog tlaka.

Infekcija počinje kada se proteini dugih šiljaka koji strše iz čestica virusa spoje na ACE2 protein stanice. Od tog trenutka, šiljak se transformira, rasklapa i ponovo sastavlja pomoću namotanih dijelova nalik opruzi koji počinju zakopani u jezgri šiljaka. Rekonfigurirani šiljak zakači se u stanicu i zajedno ruši česticu virusa i stanicu. Time se stvara kanal kroz koji niz virusnog genetskog materijala može provući put u bezazlenu stanicu.

Ilustracija proteina šiljaka SARS-CoV-2 prikazana sa strane (lijevo) i odozgo. Protein zahvaća ljudske plućne stanice. 5-HT2AR/Wikimedia

SARS-CoV-2 se prenosi s osobe na osobu bliskim kontaktom. Epidemija crkve Shincheonji u Južnoj Koreji u veljači daje dobar dokaz kako se i koliko brzo SARS-CoV-2 širi. Čini se da su jedna ili dvije osobe s virusom sjedile licem u lice vrlo blizu nezaraženih osoba nekoliko minuta odjednom u prepunoj prostoriji. U roku od dva tjedna u zemlji je bilo zaraženo nekoliko tisuća ljudi, a više od polovice infekcija u tom se trenutku moglo pripisati crkvi. Epidemija je brzo započela jer tijela javnog zdravstva nisu bila svjesna moguće epidemije i u toj fazi nisu se široko testirala. Od tada su vlasti naporno radile, a broj novih slučajeva u Južnoj Koreji stalno je padao.

Kako virus čini ljude bolesnima

SARS-CoV-2 raste u plućnim stanicama tipa II, koje luče tvar nalik sapunu koja pomaže klizanju zraka duboko u pluća, te u stanicama koje oblažu grlo. Kao i kod SARS-a, većinu štete u COVID-19, bolesti uzrokovanoj novim koronavirusom, uzrokuje imunološki sustav koji provodi obranu spaljene zemlje kako bi spriječio širenje virusa. Milijuni stanica imunološkog sustava napadaju inficirano plućno tkivo i uzrokuju ogromne količine oštećenja u procesu čišćenja virusa i svih zaraženih stanica.

Svaka lezija COVID-19 kreće se od veličine grožđa do veličine grejpa. Izazov za zdravstvene radnike koji liječe pacijente jest podržati tijelo i održavati krv kisikom dok se pluća popravljaju.

SARS-CoV-2 ima kliznu ljestvicu ozbiljnosti. Čini se da pacijenti mlađi od 10 godina lako uklanjaju virus, čini se da se većina ljudi mlađih od 40 brzo oporavi, ali stariji ljudi pate od sve težeg COVID-19. Protein ACE2 koji SARS-CoV-2 koristi kao vrata za ulazak u stanice također je važan za regulaciju krvnog tlaka i ne radi svoj posao kada virus prvi stigne tamo. To je jedan od razloga zašto je COVID-19 ozbiljniji kod osoba s visokim krvnim tlakom.

SARS-CoV-2 je dijelom ozbiljniji od sezonske gripe jer ima mnogo više načina da spriječi stanice da dozivaju imunološki sustav u pomoć. Na primjer, jedan od načina na koji stanice pokušavaju odgovoriti na infekciju je stvaranje interferona, proteina koji signalizira alarm. SARS-CoV-2 blokira to kombinacijom kamuflaže, odvajajući proteinske markere iz stanice koji služe kao signali za pomoć i konačno uništavajući sve protuvirusne upute koje stanica napravi prije nego što se mogu upotrijebiti. Zbog toga se COVID-19 može gnojiti mjesec dana, uzrokujući malu štetu svaki dan, dok većina ljudi preboli slučaj gripe za manje od tjedan dana.

Trenutačno je stopa prijenosa SARS-CoV-2 malo veća od brzine pandemije virusa gripe H1N1 iz 2009., no SARS-CoV-2 je najmanje 10 puta smrtonosniji. Prema podacima koji su sada dostupni, COVID-19 izgleda puno poput teškog akutnog respiratornog sindroma (SARS), iako je manje vjerojatno da će SARS biti ozbiljan.

Ono što se ne zna

Još uvijek postoje mnoge misterije o ovom virusu i koronavirusima općenito-nijanse kako uzrokuju bolest, način na koji stupaju u interakciju s proteinima unutar stanice, struktura proteina koji tvore nove viruse i kako neki od osnovnih strojeva za kopiranje virusa djela.

Još jedna nepoznanica je kako će COVID-19 reagirati na promjene godišnjih doba. Gripa ima tendenciju pratiti hladno vrijeme, kako na sjevernoj tako i na južnoj hemisferi. Neki drugi ljudski koronavirusi šire se na niskoj razini tijekom cijele godine, ali čini se da tada dosežu vrhunac u proljeće. No nitko zapravo ne zna sa sigurnošću zašto se ti virusi razlikuju ovisno o godišnjim dobima.

Ono što je do sada nevjerojatno u ovoj epidemiji je dobra nauka koja je tako brzo izašla na vidjelo. Istraživačka zajednica saznala je o strukturi proteina virusa i ACE2 proteina s dijelom proteina šiljaka pričvršćenim samo nešto više od mjesec dana nakon što je genetska sekvenca postala dostupna. Prvih 20 -ak godina proveo sam radeći na koronavirusu bez ikakvih koristi. To je dobro za bolje razumijevanje, sprječavanje i liječenje COVID-19.

[Saznajte činjenice o koronavirusu i najnovija istraživanja. Prijavite se na naš bilten.]

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Pokazati/sakriti riječi koje treba znati

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Antigen: molekula koju imunološki sustav može prepoznati. više

Bakterije: jednostanični, mikroskopski organizmi koji rastu i množe se posvuda na Zemlji. Oni mogu biti korisni ili štetni za životinje. više

Citokin: kemikalija koju oslobađaju stanice u imunološkom sustavu i pomaže koordinirati imunološki odgovor slanjem poruka određenim stanicama. više

Imunološki sustav: sve stanice, tkiva i organi uključeni u borbu protiv infekcije ili bolesti u tijelu. više

Mikrob: živo biće tako sićušno da bi vam trebao mikroskop da biste ga vidjeli. više

Receptor: molekula na površini stanice koja reagira na određene molekule i prima kemijske signale koje šalju druge stanice.

Prijatelj ili neprijatelj? Identificiranje osvajača i bandita

Ljudsko tijelo ima sposobnost prepoznati milijune različitih neprijatelja. Naša ugrađena "obrambena snaga" naziva se imunološki sustav. Različiti dijelovi sustava mogu stvarati stanice i moćne kemikalije zvane citokini. Ove se stanice i citokini podudaraju i uništavaju bakterije i druge napadače. Milijuni i milijuni stanica imunološkog sustava organizirani su u skupove i podskupove. Ove skupine stanica prenose informacije naprijed -natrag.

Kemijske tvari koje proizvode ove stanice funkcioniraju kao unutarnji alarmni sustav. Njihova poruka je jednostavna: „Klice su ovdje. Ubijte klice. "

Imunološki sustav ne samo da nas štiti od infekcija. Može razlikovati tjelesne stanice od onih koje pripadaju napadačima. Stanice imunološkog sustava mogu razlikovati "ja" od "ne-ja".

Svaka stanica u našem tijelu nosi posebne molekule markera. Ti se markeri nazivaju i antigeni. Oglašavaju "sebe". Zamislite tipičnu ćeliju kao naranču prekrivenu kvrgavim čačkalicama i šarenim zastavicama.

Na pravoj ćeliji ove čačkalice i zastavice su komadići proteina i drugih posebnih molekula. Jedan ili više ovih bjelančevina govori lovcima i ubojicama imunološkog sustava da je sve u redu. Alarm se oglašava kada imunološki branitelji naiđu na stanicu ili mikrob koji nema "self" marker. Sustav se pokreće kako bi se suočio s prijetnjom bolesti.

Dugotrajno pamćenje

Stanice imunološkog sustava mogu se sjetiti prošlih borbi s virusima i bakterijama koje izazivaju bolesti. Sustav vodi kemijski zapis o tome kako je prepoznao svakog napadača. Ove posebne molekule proteina nazivaju se antitijela. Protutijela su molekule u obliku slova Y. Oni odgovaraju specifičnom antigenu poput ključa u bravu. Svaka stanica ili organizam koji pokreće imunološki sustav u akciju naziva se antigen (i obično nije antigen za sebe). Antigeni mogu biti klice poput virusa ili bakterije. Ili mogu biti komadići tih klica.

Antitijela se zaključavaju na antigen. Oni služe kao zastava koja označava napadača za uništenje. Kasnije, kada sličan mikrob ponovno napadne, tijelo ga prepoznaje kao napadača. Imunološki sustav pokreće akciju. Cilj je uništiti invazivni antigen ili mikrob prije nego što se razvije u novu infekciju.

Zbog toga većina ljudi samo jednom oboli od vodenih kozica ili drugih dječjih bolesti. Imunološki sustav jednom se borio u borbi protiv ovih invazivnih klica. Cjepiva djeluju na isti način. Izlažu vaše tijelo komadima ili oslabljenim verzijama klica, a vaše tijelo uči se boriti se protiv njih. Cjepiva protiv ospica i zaušnjaka pomažu djeci da uopće ne dobiju bolest. Vaše tijelo vodi kemijski zapis i štiti vas od zaraze tim bolestima.


Reference

van Doramalen, N. et al. N. engl. J. Med. 382, 1564–1567 (2020).

Goldman, E. Lancet Infect. Dis. 20, 892–893 (2020).

Moriarty, L. F. et al. Morb. Smrtni. Wkly Rep. 69, 347–352 (2020).

Chin, A. W. H. et al. Lancet Microbe 1, E10 (2020).

Harbourt, D. E. et al. PLoS Negl. Trop. Dis. 14, e0008831 (2020).

Projekt REALM. Test 5: Prirodno slabljenje kao pristup dekontaminacije za SARS-CoV-2 na tekstilnim materijalima (REALM, 2020) dostupno na go.nature.com/3t1eycg

Ben-Shmuel, A. et al. Clin. Mikrobiol. Zaraziti. 26, 1658–1662 (2020).

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Harvey, A. P. et al. Okoliš. Sci. Technol. Lett. https://doi.org/10.1021/acs.estlett.0c00875 (2020).

Haug, N. et al. Priroda Ljudsko ponašanje. 4, 1303–1312 (2020).


Kako virusi napadaju stanice

Svako toliko vijest o izbijanju virusa postane viralna i privuče široku pozornost javnosti u medijima. Virus humane imunodeficijencije (HIV), virus Zapadnog Nila, ptičja gripa (ptičja gripa), ebola, respiratorni virus na Bliskom istoku i virus Zika postali su u žurbi naslova, emisija i intervjua u centru pažnje medija . A zatim, poput drugih kriza, blijede s vidika ostavljajući javnost s novom brigom za zdravlje zabrinutom zbog malo znanja o stvarnim čimbenicima koji su uključeni u problem. Iza kulisa, međutim, znanstvenici neprestano rade na pokušaju razumijevanja i obrane od ovih podmuklih uzročnika.

Virusi su savršeni paraziti. Desetljećima je poznato da jednom kad virus uđe u stanicu, otima stanične procese kako bi proizveo virusno kodirani protein koji će replicirati genetski materijal virusa. Virusni mehanizmi mogu translocirati proteine ​​i genetski materijal iz stanice i sastaviti ih u nove čestice virusa. Suvremena istraživanja otkrila su specifične mehanizme koje virusi koriste za ulazak u stanice i njihovu infekciju.

Pojedinačna virusna čestica, nazvana virion, daleko je jednostavnija struktura od bakterije. Često se postavljalo pitanje je li virus živ. Zasigurno se ne živi u svakodnevnom smislu riječi. Virioni se sastoje od genetskog materijala 𠅍NA ili RNA zatvorenog u proteinskoj prevlaci. Mnogi virusi, nazvani virusi s ovojnicom, imaju dodatnu vanjsku membranu koja zatvara proteinski omotač. Ova membranska ovojnica materijal je kooptiran od ćelijske vlastite membrane. Budući da novi virion izlazi iz zaražene stanice domaćina, omotan je dvoslojnom membranom stanice i sa sobom nosi bilo koji protein koji se slučajno ugradi u membranu na mjestu pupanja. Virusi u ovojnici tada mogu započeti novi ciklus infekcije spajanjem svoje ovojnice dobivene iz stanice s staničnom membranom nezaražene stanice.

Neke vrste omotanog virusa stapaju se izravno s vanjskom (plazma) membranom stanice, dok druge zahvaćaju cijela endocitoza ili slični procesi, a zatim spajaju svoju ovojnicu s membranom unutrašnje organele koja zahvaća (npr. Endosom) kako bi dobili pristup u unutrašnjost ćelije. U oba slučaja, genetski materijal virusa napao je stanicu kroz barijeru njezine membrane, a infekcija će neizbježno uslijediti (sl. ਁ). Infekcija se može spriječiti ako se spriječi fuzija virusne ovojnice sa stanicom ili endosomalnom membranom. Slično, ako se cjepivo može usmjeriti protiv fuzijskog proteina virusa, infekcija se može spriječiti. Na primjer, cjepiva protiv virusa gripe ciljaju na fuzijske proteine ​​virusa.

Putevi ulaska virusa. Virus se može stopiti izravno s plazma membranom (fuzija posredovana receptorima) ili nakon što se proguta u endosom. Koji će se od ovih načina slijediti ovisi o vrsti virusa. U fuziji s plazma membranom, virus se veže za protein u staničnoj membrani. Funkcija ovog staničnog proteina (receptora za virus, prikazana u zelena) izopačeno je da izazove konformacijsku promjenu u fuzijskom proteinu virusa, što dovodi do fuzije. Za virus koji se pokreće unutar endosoma, kisela stanja endosoma izazivaju fuziju. U oba slučaja, virusni genom prolazi kroz fuzijske pore u citosol i započinje infekcija. Idite na internet da biste vidjeli ovu brojku u boji.

Virusni genetski materijal relativno je mali i kodira samo nekoliko proteina. Svi virusi s ovojnicom sadrže fuzijske proteine, molekule odgovorne za spajanje ovojnice s staničnom membranom. Ovi proteini su izvedeni iz virionske genetske sekvence. Precizan genetski materijal, niz aminokiselina i detalji u strukturi fuzijskog proteina jedinstveni su za svaku vrstu virusa. Slijedom toga, antivirusni lijekovi širokog spektra ne postoje, pa je za svaku vrstu virusa tipično potrebno razviti posebna cjepiva i lijekove. Virusna površina pojedinog viriona sadrži više kopija njegova fuzijskog proteina. Na primjer, virus gripe obično sadrži 500 � kopija, dok HIV sadrži samo desetak kopija (1, 2). Strojevi viriona toliko su učinkoviti da svaka stanica zaražena čak i jednim virionom može proizvesti oko milijun novih viriona. Budući da virusi s ovojnicom koriste slične mehanizme za isporuku genetskog materijala u stanice, možda postoje načini za sprječavanje infekcije prije ulaska virusa koji bi bili učinkoviti za veliki broj različitih virusa.

Membrana koja je koža stanice i virion omotan, te je ulaz za ulazak virusa, sastoji se od lipida i proteina. Lipidi su otprilike linearne molekule masti koje su s jednog kraja vezane za glavnu skupinu topljivu u vodi. Lipidi osiguravaju koheziju koja održava biološke membrane netaknutima. Spontano se raspoređuju u lipidni dvosloj jer se masna mast ne miješa s vodom. Zaglavne skupine jednog jednoslojnog sloja okrenute su prema vanjskoj vodenoj otopini, dok su zaglavne skupine drugog sloja okrenute prema unutrašnjosti stanice. Integralni membranski proteini, poput virusnih fuzijskih proteina, umetnuti su u dvosloj i izbacuju se s površine lipida u vanjske sante poput otopine. Membrane su općenito 50% lipida i 50% proteina po težini, ali proteini su mnogo teži od lipida, pa se u membrani nalazi oko sto puta više lipida nego proteina. Membrane se mogu stopiti jedna s drugom jer su tekućine (3), a lipidi daju fluidnost membrani.

Virusi se u početku lijepe za stanične membrane interakcijama koje nisu povezane sa fuzijskim proteinima. Virus surfa uz tekućinsku površinu stanice i na kraju se virusni fuzijski proteini vežu za molekule receptora na staničnoj membrani (4). Kad bi došlo samo do vezanja, dvije bi membrane ostale različite. Fuzija se ne događa spontano jer su dvoslojevi stabilni. Fuzijski proteini obavljaju posao potičući lipide iz njihove početne dvoslojne konfiguracije. Ti proteini uzrokuju diskontinuitete u dvoslojima koji izazivaju povezivanje lipida jedne membrane (npr. Virusne ovojnice) s lipidima druge (npr. Stanične membrane), pretvarajući dva dvosloja u jedan.

Fuzija se odvija u dva glavna koraka (slika ਂ). Prvo, dva jednoslojna sloja sa suprotnih membrana koji se međusobno dodiruju  merge, proces poznat kao “hemifusion. ” Dva nesložena jednoslojna sloja međusobno se stvaraju jedan dvosloj, poznat kao hemifuzijska dijafragma, koja nastavlja sprječavati virusni genom od ulaska u citosol. U drugom koraku, fuzijski proteini ometaju ovaj jednoslojni sloj kako bi stvorili pore koje osiguravaju vodeni put između virusa i unutrašnjosti stanice. Kroz ovu fuzijsku pora virusni genom ulazi u stanicu i započinje infekciju.

Koraci fuzije. Virus se veže na određene receptore (svaki je ilustriran kao mali kaktus) na staničnoj membrani. U početku su četiri jednoslojna sloja (u plava) odvojite dva unutarnja vodena odjeljka. Nakon što se fuzijski peptidi umetnu u ciljnu membranu, jednoslojni slojevi koji su okrenuti jedan prema drugom se spajaju i brišu iz spojenog područja. Nekontaktni jednoslojevi savijaju se u očišćeno područje i dolaze u međusobni kontakt, tvoreći novu dvoslojnu membranu poznatu kao hemifuzijska dijafragma. U ovom trenutku (hemifuzija), samo dva jednoslojna sloja odvajaju odjeljke. Fuzijski protein djeluje kao orah koji prisiljava stvaranje pora unutar polufuzijske dijafragme. Time se uspostavlja kontinuitet između dva vodena odjeljka i fuzija je završena. Idite na internet da biste vidjeli ovu brojku u boji.

Čini se da hemifuzija i stvaranje pora zahtijevaju usporedive količine rada, ali točna količina energije potrebna za svaki korak još nije poznata (5). Ovi energetski detalji mogu biti važni jer što je više rada potrebno za postizanje koraka, lakše će biti farmakološki blokirati taj korak. Ovu energiju opskrbljuju virusni fuzijski proteini, koji su u biti molekularni strojevi. Neki se njihovi dijelovi kreću na velike udaljenosti tijekom koraka fuzije. Fuzijski proteini mogu se smatrati složenim sklopom ključeva, kliješta, bušilica i drugih mehaničkih alata.

Budući da fuzija nije spontana, unutar dvosloja moraju se privremeno stvoriti diskontinuiteti koji omogućuju vodi da dospije u masnu, uljnu unutrašnjost membrane. Čak je i kratkotrajna izloženost male mrlje masne unutrašnjosti vodi energetski skupo. Slično, stvaranje pora u polufuzijskoj membrani zahtijeva izlaganje unutrašnjosti dvosloja vodi (6). Nasuprot tome, proširenju pora nije potrebna takva izloženost. Ipak, proširenje pora zahtijeva najviše rada u procesu fuzije.

Energija je također potrebna zbog drugog temeljnog svojstva dvoslojnih membrana. Iako su dvoslojevi tekući, ne ponašaju se u potpunosti poput vode ili ulja jer ne poprimaju oblik svoje posude. Biological membranes have shapes that are determined by their precise lipids and the proteins associated with them (7). Work is required to force membranes out of their spontaneous shape, which is the shape of lowest energy. The fusion pore that connects the virus and cell is roughly an hourglass shape (8). The wall of a fusion pore is a membrane with components that are a mixture of the two original membranes. An hourglass shape deviates significantly from the spontaneous shape of the initial membranes that constitute the pore. The greater the diameter of the pore, the greater is the area of the lining membrane, and so pore expansion is a highly energy consuming process. Viral genetic material, the genome, is rather large, on the order of � nm. The initial fusion pore is only 𢏁 nm, so considerably more membrane must line a pore as it enlarges to a size sufficient to allow passage of a viral genome from a virus to a cell interior. In fact, it appears that more energy is required for pore expansion than for hemifusion or pore formation.

All viral fusion proteins contain a greasy segment of amino acids, referred to as a fusion peptide or fusion loop. Soon after activation of the fusion protein, the fusion peptide inserts into the target membrane (either plasma or endosomal). At this point, two extended segments of amino acidsਊre anchored to the membranes: the fusion peptides in the target membrane and the membrane-spanning domains of the fusion proteins in the viral envelope ( Fig.ਂ ). The fusion proteins continue to reconfigure, causing the two membrane-anchored domains to come toward each other. This pulls the viral envelope and cellular membrane closely together (9). The fusion proteins exert additional forces, but exactly what these forces are and how they promote fusion remains unknown.

An initial step in a cell’s digestive system is to internalize extracellular materials through engulfment by endosomes. A virion engulfed into an endosome is like a Trojan horse, because the cell perceives the virus particle as food. Endosomes become increasingly acidified as they move from the cell surface further into the cell’s interior. Fusion of viruses within endosomes depends critically on the acidic environment. By breaking molecular bonds, acid triggers the conformational changes in the fusion protein that lead to the sequential steps of membrane fusion.

The hemifusion diaphragm is a bilayer membrane that is unusual in that each of its lipid monolayers is derived from different membranes, and it does not contain any membrane-spanning proteins (10). Several copies of the fusion protein within a virus are required to induce both hemifusion and pore formation. During hemifusion, the proteins form a ring just outside the diaphragm and act cooperatively to create stresses that lead to a local rupture in the diaphragm, thereby creating the initial fusion pore. The universality of this mechanism is remarkable when one considers that the primary amino acid sequences and structures of fusion proteins are quite diverse.

Influenza, HIV, and Ebola are enveloped viruses of significant public health concern. Each virus encodes a unique fusion protein: hemagglutinin (HA) for influenza, envelope glycoproteins for HIV (Env), and glycoprotein for Ebola (GP).

The earliest descriptions of an illness that was likely influenza were written in the 1500s and were called �tarrhal fever” (11). The flu pandemic of 1918 resulted in the deaths of some 20 million people and arguably accelerated the end of World War I (12). Flu pandemics have continued to occur periodically, as they did in 1947, 1957, 1968, and 2009, but were far less deadly.

Influenza virus is not free to infect other cells upon budding because HA binding to specific sugars, sialic acids, that protrude from cell surfaces prevents a virus from freeing itself from the cell. Another envelope protein, neuraminidase (NA), cleaves sialic acids off the cell, setting the influenza free. Drugs that are NA inhibitors, such as the well-known Tamiflu (oseltamivir), stop further infection within an individual by eliminating the cleavage of sialic acids (13).

Research efforts for influenza, HIV, and Ebola virus have focused on targeting their fusion proteins. But particular properties of the viruses and their proteins have hindered the successful development of vaccines that protect against infection.

Standard vaccines against envelope viruses prime the immune system to generate antibodies (Abs) against the envelope proteins. In the case of influenza, Ab binding is mainly to HA, and secondarily to NA. Abs bind to exposed outer portions of envelope proteins and are large, thereby hindering close engagement of the virus with a cell membrane. Some antigenic sites surround an indented pocket within the surface of HA that is responsible for binding sialic acids on cell surfaces. Abs thus block the binding of HA to plasma membranes, eliminating the membrane fusion that leads to infection. HA readily mutates, and although the accumulated individual mutations lead to only small changes in the conformation of HA, these mutations greatly reduce binding of Abs to HA. Hence, a new vaccine must be developed each year (14).

Influenza presents another problem: its genome is not one਌ontinuous strand of RNA, like most viruses, but is segmented into multiple strands. Segmentation allows the genes for HA and NA to reassort: the RNA strands of different flu viruses—such as genes from an avian flu virus and a mammalian flu virus𠅌ombine to make what is essentially a new virus. Reassorted viruses are described in terms of HA and NA types and are termed H1N1, H3N2, H5N1, and so forth. Some reassortments cause periodic influenza pandemics that are characterized by an unusually large number of severe, and sometimes fatal, infections (15).

HIV-1 is clinically, to date, the most important retrovirus. Retroviruses transcribe RNA into DNA in a process called reverse transcription, and the viral DNA is incorporated into the genome of the host cell. HIV is a relatively recent emerging virus, appearing in the last 70 years or so. It has independently jumped to humans at least four times, probably due to the bush meat trade of gorillas and chimpanzees, and from chimps kept as pets (16). Currently, � million people are infected, with about two-thirds of them living in Sub-Saharan Africa. Viruses not only cause diseases, but have also been important in evolution. Retroviruses can move large gene segments from one organism to another, and some 100,000 pieces of retroviral DNA make up 𢏈% of the human genome (17).

The traditional approach of using attenuated or inactivated virus, and by extension, envelope proteins, as vaccines has been ineffective against HIV-1 for a number of reasons. The fidelity of the reverse transcriptase of HIV-1 is low and therefore mutations in the viral protein occur frequently. As a result, HIV-1 Env mutates so rapidly that it quickly evades a static vaccine. Furthermore, Env is highly glycosylated, effectively sugarcoating the exposed portion of the protein, and Abs do not bind well to sugars. There is a small unglycosylated region on the surface of Env, and efforts were directed against this bald spot but did not lead to clinically effective approaches. Many nontraditional vaccine approaches have been developed and tested and these efforts continue, but none have yet been sufficiently successful. Modern biology and public health measures have combined to develop positive methods to prevent and treat the acquired immunodeficiency syndrome.

Antiretroviral therapies have largely eliminated the progression of viral infection to AIDS in individuals for whom these therapies have been available. Relatively soon after HIV-1 was identified, blood supplies were able to be accurately screened for HIV contamination. This was achieved only because prior advancements in the biological sciences allowed the development of new diagnostic methods that were sensitive enough to detect HIV. More recently it has been shown that HIV infection can be eliminated from the body: the Berlin Patient infected with HIV (and suffering from leukemia) received a stem cell transplant and was thereafter free of the virus (18).

The recent Ebola outbreak was caused by the deadliest of the three types of Ebola virus strains known to infect humans, with a fatality rate exceeding 50%. It typically takes 𢏄�ꃚys from the time of infection to the appearance of symptoms, but symptoms can manifest in as little as 2ꃚys or as long as 3 weeks. It appears that with Ebola, unlike influenza, infected individuals do not become contagious until they exhibit symptoms. Trial vaccines using virus inactivated by traditional methods have proven unsuccessful, but viruses using recombinant technologies are showing considerable promise. Several other approaches may also be effective, including a cocktail of humanized murine monoclonal Abs, which have been shown to be statistically effective in protecting nonhuman primates.

Acidification of endosomes causes Ebola fusion in an unusual manner. Influenza HA, HIV-1 Env, and Ebola GP are cleaved into two subunits before viral-cell binding. This cleavage confers to HA and Env the full ability to induce fusion. In contrast, Ebola GP must be cleaved at an additional site to cause fusion. This cleavage occurs within endosomes by a protease (cathepsin) that is effective at low pH (19). A conformational change ensues, allowing Ebola GP to bind to an endosomal receptor, Niemann-Pick type C1. Binding activates GP, and a merger between the viral and endosomal membranes then proceeds. The identification of Niemann-Pick type C1 as a receptor opens up a new potential target for a small molecule drug to block binding and prevent infection (20).

The most reliable way to prevent infection caused by any virus is to eliminate entry in the first place. Intellectual and technological progress has been great, but recurrent viral outbreaks highlight the need for more innovative approaches. In addition to the proteins responsible for viral entry, many other targets are being explored, including genetic variations that increase susceptibility to infection, proteins that bind to viral proteins, and host immunity proteins. Genomic and proteomic analysis of cellular factors and their interactions, manipulation of experimental animals, live cell and molecular imaging, and analysis and integration of protein and gene data sets will identify host factors that viruses exploit in their life cycle. Because viruses make use of cellular machinery𠅊nd invariably do so in a streamlined and robust manner𠅏uture viral studies will provide new understandings that will apply not only to virally induced diseases but to other diseases as well. Biophysics has been an integral part of understanding viral entry mechanisms, which have brought new insights and discoveries that just a few years ago could not have been imagined.


Hydrophobic proteins on virus surfaces can help purify vaccines

A person doesn't have to get sick to catch a virus. Researchers hope to catch viruses for detection and vaccinations by understanding their sticky outer layers.

The complex structures making the surface of a virus are small weaves of proteins that make a big impact on how a virus interacts with cells and its environment. A slight change in protein sequence makes this surface slightly water-repelling, or hydrophobic, causing it to stick to other hydrophobic surfaces. A new paper, published recently in Colloids and Surfaces B: Biointerfaces, details surface hydrophobicity in porcine parovirus (PPV).

Caryn Heldt, an associate professor of chemical engineering at Michigan Technological University, is the paper's lead author. Currently, she is on sabbatical in St. Louis working with Pfizer to better understand how surface hydrophobicity could be used to improve vaccination production.

"Vaccine purification is all about surface interactions if the components break apart, then they cannot be used as a therapeutic," Heldt says, adding that sensing and removing viruses also depend on surface interactions. "This may also help biologists understand a virus' interactions with a cell."

The main finding in this paper is that Heldt and her team compared experimental methods with computational methods to measure the surface chemistry.

Because virus hydrophobicity is relatively new and difficult to measure, Heldt's team focused on using hydrophobicity models as a comparison. They compared the expected hydrophobicity measurements based on the main protein from the virus, the non-enveloped PPV, to well-studied model proteins that span a range of repelling or attracting water. Then they analyzed the samples using two kinds of chromatography -- the analysis of chemical mixtures -- along with fluorescent dyes that illuminate sticky, hydrophobic patches on the proteins.

The key is that the measurements focus on what's easy to reach. These locations are part of what's called a crystal structure's solvent accessible surface area. Narrowing down the observed area in an experiment helped the team measure hydrophobicity.

"The entire virus capsid is too large of a complex to do these calculations," Heldt says, explaining the capsid is an outside shell made of 60 copies of similar proteins -- VP1, VP2, VP3 -- and her team tested the exposed parts of VP2, which is the most abundant. "It was interesting that we were still able to correlate our solvent exposed surface area calculations with the experimental results because we were only using this one protein."

The strong correlation between the computational and experimental results indicates that PPV -- and likely other viruses -- have a measurable hydrophobicity. Once the measurements are better understood, then Heldt and other researchers can better catch viruses. Doing so can improve detecting viruses, concentrating them and purifying vaccines.


Viruses: You've heard the bad here's the good

"The word, virus, connotes morbidity and mortality, but that bad reputation is not universally deserved," said Marilyn Roossinck, PhD, Professor of Plant Pathology and Environmental Microbiology and Biology at the Pennsylvania State University, University Park. "Viruses, like bacteria, can be important beneficial microbes in human health and in agriculture," she said. Her review of the current literature on beneficial viruses appeared ahead of print April 24 in the Journal of Virology, which is published by the American Society for Microbiology.

In sharp contrast to the gastrointestinal distress it causes in humans, the murine (mouse infecting) norovirus plays a role in development of the mouse intestine and its immune system, and can actually replace the beneficial effects of certain gut bacteria when these have been decimated by antibiotics. Normal, healthy gut bacteria help prevent infection by bacteria that cause gastrointestinal illness, but excessive antibiotic intake can kill the normal gut flora, and make one vulnerable to gastrointestinal disease. However, norovirus infection of mice actually restored the normal function of the immune system's lymphocytes and the normal morphology of the intestine, said Roossinck.

Mammalian viruses can also provide immunity against bacterial pathogens. Gamma-herpesviruses boost mice resistance to Listeria monocytogenes, an important human gastrointestinal pathogen, and to Yersinia pestis, otherwise known as plague. "Humans are often infected with their own gamma-herpes viruses, and it is conceivable that these could provide similar benefits," said Roossinck.

Latent herpesviruses also arm natural killer cells, an important component of the immune system, which kill both mammalian tumor cells, and cells that are infected with pathogenic viruses.

The gastrointestinal tracts of mammals are plush with viruses. So far, little is known about how these viruses affect their hosts, but their sheer number and diversity suggest that they have important functions, said Roossinck. For example, GI viruses that infect bacteria--known as phage--may modulate expression of bacterial genes involved in host digestion.

Recent research shows that bacteriophage stick to the mucus membranes of many metazoans (the class "Animalia," which includes everything from worms to wombats). And mucus membranes, Roossinck points out, are the points of entry for many bacterial pathogens, suggesting that they provide the first line of defense against invading bacteria.

Viruses also provide a variety of services for plants. A few plants grow in the hot soils surrounding the geysers and the "Artists' Paintpots" of Yellowstone National Park. One such plant, which is a type of tropical panic grass, is a symbiosis that includes a fungus that colonizes the plant, and a virus that infects that fungus. All three members of this symbiosis are necessary for survival in soils simmering at more than 122 degrees Fahrenheit.

In the laboratory, Roossinck has created symbioses between the same virus-infected fungus and other plants. This has enabled every plant her group has tested to survive at these elevated soil temperatures, including tomato, she says, noting that she has pushed the soil temperature to 140 degrees without killing the plant.

Investigators have also found that certain viruses can render some plants drought tolerant, and at least one example of virally-conferred cold tolerance has been discovered-- discoveries that could become useful for expanding the ranges of crops.

Plants are often infected with "persistent viruses" that are passed down from generation to generation, perhaps over thousands of years, with viruses that are transmitted to nearly 100 percent of their plant progeny, but that have never been shown to be transmitted from one plant to another. "One such virus, white clover crytpic virus, suppresses formation of nitrogen-fixing nodules when adequate nitrogen is present in the soil, saving the plant from producing a costly organ when it is not needed" said Roossinck.

Other beneficial viruses are the ancient retroviruses that long ago made a permanent home in the genome, or that left genes therein, said Roossinck. "The mammalian genes for syncitin, essential in the establishment of the placenta, are retroviral env genes that were incorporated on several different occasions," Roossinck writes. "They even function differently in ruminants compared to other mammals. these elements are considered viral fossils that can help us understand the deep evolution of viruses."

"Viruses are beyond a doubt the coolest things I have ever encountered," said Roossinck. "They do truly amazing things with very little genetic information. I was always a little disturbed at the bad rap they get, so it was very exciting for me to find good ones."


Sadržaj

CAMs are classified into four major families: integrins, immunoglobulin (Ig) superfamily, cadherins, and selectins. [2] Cadherins i IgSF are homophilic CAMs, as they directly bind to the same type of CAMs on another cell, while integrini i selectins are heterophilic CAMs that bind to different types of CAMs. [2] [ potreban je citat ] Each of these adhesion molecules has a different function and recognizes different ligands. Defects in cell adhesion are usually attributable to defects in expression of CAMs.

In multicellular organisms, bindings between CAMs allow cells to adhere to one another and creates structures called cell junctions. According to their functions, the cell junctions can be classified as: [1]

  • Anchoring junctions (adherens junctions, desmosomes and hemidesmosomes), which maintain cells together and strengthens contact between cells.
  • Occluding junctions (tight junctions), which seal gaps between cells through cell–cell contact, making an impermeable barrier for diffusion
  • Channel-forming junctions (gap junctions), which links cytoplasm of adjacent cells allowing transport of molecules to occur between cells
  • Signal-relaying junctions, which can be synapses in the nervous system

Alternatively, cell junctions can be categorised into two main types according to what interacts with the cell: cell–cell junctions, mainly mediated by cadherins, and cell–matrix junctions, mainly mediated by integrins.

Cell–cell junctions Edit

Cell–cell junctions can occur in different forms. In anchoring junctions between cells such as adherens junctions and desmosomes, the main CAMs present are the cadherins. This family of CAMs are membrane proteins that mediate cell–cell adhesion through its extracellular domains and require extracellular Ca 2+ ions to function correctly. [2] Cadherins forms homophilic attachment between themselves, which results in cells of a similar type sticking together and can lead to selective cell adhesion, allowing vertebrate cells to assemble into organised tissues. [1] Cadherins are essential for cell–cell adhesion and cell signalling in multicellular animals and can be separated into two types: classical cadherins and non-classical cadherins. [2]

Adherens junctions Edit

Adherens junctions mainly function to maintain the shape of tissues and to hold cells together. In adherens junctions, cadherins between neighbouring cells interact through their extracellular domains, which share a conserved calcium-sensitive region in their extracellular domains. When this region comes into contact with Ca 2+ ions, extracellular domains of cadherins undergo a conformational change from the inactive flexible conformation to a more rigid conformation in order to undergo homophilic binding. Intracellular domains of cadherins are also highly conserved, as they bind to proteins called catenins, forming catenin-cadherin complexes. These protein complexes link cadherins to actin filaments. This association with actin filaments is essential for adherens junctions to stabilise cell–cell adhesion. [10] [11] [12] Interactions with actin filaments can also promote clustering of cadherins, which are involved in the assembly of adherens junctions. This is since cadherin clusters promote actin filament polymerisation ,which in turn promotes the assembly of adherens junctions by binding to the cadherin–catenin complexes that then form at the junction. [ potreban je citat ]

Desmosomes Edit

Desmosomes are structurally similar to adherens junctions but composed of different components. Instead of classical cadherins, non-classical cadherins such as desmogleins and desmocollins act as adhesion molecules and they are linked to intermediate filaments instead of actin filaments. [13] No catenin is present in desmosomes as intracellular domains of desmosomal cadherins interact with desmosomal plaque proteins, which form the thick cytoplasmic plaques in desmosomes and link cadherins to intermediate filaments. [14] Desmosomes provides strength and resistance to mechanical stress by unloading forces onto the flexible but resilient intermediate filaments, something that cannot occur with the rigid actin filaments. [13] This makes desmosomes important in tissues that encounter high levels of mechanical stress, such as heart muscle and epithelia, and explains why it appears frequently in these types of tissues.

Tight junctions Edit

Tight junctions are normally present in epithelial and endothelial tissues, where they seal gaps and regulate paracellular transport of solutes and extracellular fluids in these tissues that function as barriers. [15] Tight junction is formed by transmembrane proteins, including claudins, occludins and tricellulins, that bind closely to each other on adjacent membranes in a homophilic manner. [1] Similar to anchoring junctions, intracellular domains of these tight junction proteins are bound with scaffold proteins that keep these proteins in clusters and link them to actin filaments in order to maintain structure of the tight junction. [16] Claudins, essential for formation of tight junctions, form paracellular pores which allow selective passage of specific ions across tight junctions making the barrier selectively permeable. [15]

Gap junctions Edit

Gap junctions are composed of channels called connexons, which consist of transmembrane proteins called connexins clustered in groups of six. [17] Connexons from adjacent cells form continuous channels when they come into contact and align with each other. These channels allow transport of ions and small molecules between cytoplasm of two adjacent cells, apart from holding cells together and provide structural stability like anchoring junctions or tight junctions. [1] Gap junction channels are selectively permeable to specific ions depending on which connexins form the connexons, which allows gap junctions to be involved in cell signalling by regulating the transfer of molecules involved in signalling cascades. [18] Channels can respond to many different stimuli and are regulated dynamically either by rapid mechanisms, such as voltage gating, or by slow mechanism, such as altering numbers of channels present in gap junctions. [17]

Adhesion mediated by selectins Edit

Selectins are a family of specialised CAMs involved in transient cell–cell adhesion occurring in the circulatory system. They mainly mediate the movement of white blood cells (leukocytes) in the bloodstream by allowing the white blood cells to "roll" on endothelial cells through reversible bindings of selections. [19] Selectins undergo heterophilic bindings, as its extracellular domain binds to carbohydrates on adjacent cells instead of other selectins, while it also require Ca 2+ ions to function, same as cadherins. [1] cell–cell adhesion of leukocytes to endothelial cells is important for immune responses as leukocytes can travel to sites of infection or injury through this mechanism. [20] At these sites, integrins on the rolling white blood cells are activated and bind firmly to the local endothelial cells, allowing the leukocytes to stop migrating and move across the endothelial barrier. [20]

Adhesion mediated by members of the immunoglobulin superfamily Edit

The immunoglobulin superfamily (IgSF) is one of the largest superfamily of proteins in the body and it contains many diverse CAMs involved in different functions. These transmembrane proteins have one or more immunoglobulin-like domains in their extracellular domains and undergo calcium-independent binding with ligands on adjacent cells. [21] Some IgSF CAMs, such as neural cell adhesion molecules (NCAMs), can perform homophilic binding while others, such as intercellular cell adhesion molecules (ICAMs) or vascular cell adhesion molecules (VCAMs) undergo heterophilic binding with molecules like carbohydrates or integrins. [22] Both ICAMs and VCAMs are expressed on vascular endothelial cells and they interact with integrins on the leukocytes to assist leukocyte attachment and its movement across the endothelial barrier. [22]

Cell–matrix junctions Edit

Cells create extracellular matrix by releasing molecules into its surrounding extracellular space. Cells have specific CAMs that will bind to molecules in the extracellular matrix and link the matrix to the intracellular cytoskeleton. [1] Extracellular matrix can act as a support when organising cells into tissues and can also be involved in cell signalling by activating intracellular pathways when bound to the CAMs. [2] Cell–matrix junctions are mainly mediated by integrins, which also clusters like cadherins to form firm adhesions. Integrins are transmembrane heterodimers formed by different α and β subunits, both subunits with different domain structures. [23] Integrins can signal in both directions: inside-out signalling, intracellular signals modifying the intracellular domains, can regulate affinity of integrins for their ligands, while outside-in signalling, extracellular ligands binding to extracellular domains, can induce conformational changes in integrins and initiate signalling cascades. [23] Extracellular domains of integrins can bind to different ligands through heterophilic binding while intracellular domains can either be linked to intermediate filaments, forming hemidesmosomes, or to actin filaments, forming focal adhesions. [24]

Hemidesmosomes Edit

In hemidesmosomes, integrins attach to extracellular matrix proteins called laminins in the basal lamina, which is the extracellular matrix secreted by epithelial cells. [1] Integrins link extracellular matrix to keratin intermediate filaments, which interacts with intracellular domain of integrins via adapter proteins such as plectins and BP230. [25] Hemidesmosomes are important in maintaining structural stability of epithelial cells by anchoring them together indirectly through the extracellular matrix.

Focal adhesions Edit

In focal adhesions, integrins attach fibronectins, a component in the extracellular matrix, to actin filaments inside cells. [24] Adapter proteins, such as talins, vinculins, α-actinins and filamins, form a complex at the intracellular domain of integrins and bind to actin filaments. [26] This multi-protein complex linking integrins to actin filaments is important for assembly of signalling complexes that act as signals for cell growth and cell motility. [26]

Eukarioti Edit

Plants cells adhere closely to each other and are connected through plasmodesmata, channels that cross the plant cell walls and connect cytoplasms of adjacent plant cells. [27] Molecules that are either nutrients or signals required for growth are transported, either passively or selectively, between plant cells through plasmodesmata. [27]

Protozoans express multiple adhesion molecules with different specificities that bind to carbohydrates located on surfaces of their host cells. [28] cell–cell adhesion is key for pathogenic protozoans to attach en enter their host cells. An example of a pathogenic protozoan is the malarial parasite (Plasmodium falciparum), which uses one adhesion molecule called the circumsporozoite protein to bind to liver cells, [29] and another adhesion molecule called the merozoite surface protein to bind red blood cells. [30]

Pathogenic fungi use adhesion molecules present on its cell wall to attach, either through protein-protein or protein-carbohydrate interactions, to host cells [31] or fibronectins in the extracellular matrix. [32]

Prokaryotes Edit

Prokaryotes have adhesion molecules on their cell surface termed bacterial adhesins, apart from using its pili (fimbriae) and flagella for cell adhesion. [8] Adhesins can recognise a variety of ligands present on the host cell surfaces and also components in the extracellular matrix. These molecules also control host specificity and regulate tropism (tissue- or cell-specific interactions) through their interaction with their ligands. [33]

Uređivanje virusa

Viruses also have adhesion molecules required for viral binding to host cells. For example, influenza virus has a hemagglutinin on its surface that is required for recognition of the sugar sialic acid on host cell surface molecules. [34] HIV has an adhesion molecule termed gp120 that binds to its ligand CD4, which is expressed on lymphocytes. [35] Viruses can also target components of cell junctions to enter host cells, which is what happens when the hepatitis C virus targets occludins and claudins in tight junctions to enter liver cells. [9]

Dysfunction of cell adhesion occurs during cancer metastasis. Loss of cell–cell adhesion in metastatic tumour cells allows them to escape their site of origin and spread through the circulatory system. [5] One example of CAMs deregulated in cancer are cadherins, which are inactivated either by genetic mutations or by other oncogenic signalling molecules, allowing cancer cells to migrate and be more invasive. [6] Other CAMs, like selectins and integrins, can facilitate metastasis by mediating cell–cell interactions between migrating metastatic tumour cells in the circulatory system with endothelial cells of other distant tissues. [36] Due to the link between CAMs and cancer metastasis, these molecules could be potential therapeutic targets for cancer treatment.

There are also other human genetic diseases caused by an inability to express specific adhesion molecules. An example is leukocyte adhesion deficiency-I (LAD-I), where expression of the β2 integrin subunit is reduced or lost. [37] This leads to reduced expression of β2 integrin heterodimers, which are required for leukocytes to firmly attach to the endothelial wall at sites of inflammation in order to fight infections. [38] Leukocytes from LAD-I patients are unable to adhere to endothelial cells and patients exhibit serious episodes of infection that can be life-threatening.

An autoimmune disease called pemphigus is also caused by loss of cell adhesion, as it results from autoantibodies targeting a person's own desmosomal cadherins which leads to epidermal cells detaching from each other and causes skin blistering. [39]

Pathogenic microorganisms, including bacteria, viruses and protozoans, have to first adhere to host cells in order to infect and cause diseases. Anti-adhesion therapy can be used to prevent infection by targeting adhesion molecules either on the pathogen or on the host cell. [40] Apart from altering the production of adhesion molecules, competitive inhibitors that bind to adhesion molecules to prevent binding between cells can also be used, acting as anti-adhesive agents. [41]


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