I-Biology Yama-Molecular Yama-RNA Virus
Ama-virus e-RNA ayiqembu lama-virus aqukethe izakhi zofuzo ze-ribonucleic acid (RNA). Leli qembu lihlanganisa amagciwane amaningi abalulekile kubantu, ezilwaneni nasezitshalweni, njenge-influenza, i-dengue, i-hepatitis C, i-polio, i-rabies, i-measles, kanye ne-SARS-CoV-2. Ukuhluka kwama-virus e-RNA kusezindleleni zawo zokuphindaphinda, amazinga aphezulu okuguquka, kanye namasu okugwema isimiso somzimba sokuzivikela somzimba esiphethe. Ukuqonda i-biology yama-molecule ama-virus e-RNA kubalulekile ekuthuthukiseni imijovo, imithi yokulwa namagciwane, kanye nezinhlelo zokuthola izifo.
1. Isakhiwo se-genome kanye nokuhleleka kwamagciwane e-RNA
Ngokuvamile, ama-genome egciwane le-RNA angaba yi-single-stranded (ssRNA) noma i-double-stranded (dsRNA). Ku-ssRNA, i-genome ingaba yi-positive-sense (+RNA) noma i-negative-sense (−RNA). Ama-virus e-+RNA anama-genome angasebenza ngqo njenge-mRNA, ngakho-ke ahunyushwa ngokushesha yi-ribosomes yeseli lomsingathi ngemva kokungena ku-cytoplasm. Izibonelo zifaka phakathi i-Picornaviridae (isb., i-poliovirus) kanye ne-Flaviviridae (isb., i-dengue). Ngokuphambene nalokho, ama-virus e-−RNA (isb., i-influenza kanye ne-rabies) aphethe ama-genome ahambisana ne-mRNA, ngakho-ke kumele aqale ahunyushwe abe yi-mRNA ngama-enzyme egciwane ngaphambi kokuba ahunyushwe.
Ama-genome egciwane le-RNA nawo angahlukaniswa noma angahlukaniswa. Umkhuhlane une-genome ehlukaniswe, evumela "ukuhlelwa kabusha," ukushintshana kwezingxenye phakathi kwamagciwane lapho kutheleleka iseli elifanayo. Lesi simo singakhiqiza izinhlobo ezintsha ezingaba nomthelela wokuqubuka okukhulu. Okwamanje, amagciwane amaningi e-RNA ane-genome eyodwa, ende evame ukufaka ikhodi ye-polyprotein, bese ihlukaniswa ibe amaprotheni asebenzayo.
Ngaphezu kokulandelana kokubhala amaprotheni (open reading frames/ORFs), ama-RNA viral genomes aqukethe izinto ezingabhalisi emaphethelweni angu-5' no-3' ezibalulekile ekuphindaphindweni kwe-RNA, ekuhumusheni nasekuzinzeni. Izakhiwo zesibili ezifana nama-hairpin nama-pseudoknot zivame ukukhombisa ukubopha kwamaprotheni egciwane kanye nezinto zeseli lomsingathi.
2. Ukungena kwegciwane kanye nokukhululwa kwe-genome (ukuvula ungqimba)
Umjikelezo wokuphila wegciwane le-RNA uqala lapho libopha i-receptor yobuso beseli lomsingathi. Lokhu kusebenzisana kunquma i-tissue tropism kanye nokucaciswa komsingathi. Ngemva kokunamathela, igciwane lingena nge-endocytosis noma i-membrane fusion. Amagciwane afihliwe, njenge-influenza kanye ne-coronavirus, ngokuvamile asebenzisa i-membrane fusion, kuyilapho amagciwane amaningi angafihliwe angena nge-endocytosis bese eshintsha isimo ukuze akhulule i-capsid yawo.
Inqubo yokuvula uqweqwe—ukukhishwa kwe-genome ye-RNA kusuka ku-capsid—iyisinyathelo esibalulekile. Uma i-RNA ingakhishwa endaweni efanele nangesikhathi esifanele, ukuphindaphinda ngeke kwenzeke. Kwamanye amagciwane, i-pH ephansi ku-endosome ibangela izinguquko esakhiweni samaprotheni egciwane, okuvumela i-genome ukuba ibalekele ku-cytoplasm.
3. Ukuhumusha: indlela amagciwane asebenzisa ngayo ama-ribosome abanikazi
Ngenxa yokuthi amagciwane awanawo ama-ribosome, athembele emishinini yokuhumusha yeseli eliphethe. Amagciwane e-RNA angahunyushwa ngqo, kodwa kumele anqobe izithiyo eziningana: ukuncintisana ne-mRNA yeseli, isidingo "sesivalo" ekugcineni kwe-5', kanye nezindlela zokulawula ikhwalithi yeseli.
Amanye amagciwane ane-end engu-5' evalwe njenge-host mRNA (isb., ama-coronavirus), kanti amanye asebenzisa amasu ahlukile, njenge-internal ribosome entry site (IRES) kuma-picornavirus, okuvumela i-ribosome ukuthi iqale ukuhumusha ngaphandle kwe-cap. Amagciwane, njenge-influenza, nawo asebenzisa "ukuhlwitha i-cap," eba i-cap ku-host mRNA ukuze ayisebenzise ku-viral mRNA yawo. Lawa maqhinga abalulekile ku-molecule biology yamagciwane e-RNA, njengoba engaba yizithako ezingaba khona zemithi yokulwa namagciwane.
Kuma-virus amaningi e-RNA, i-genome ihunyushwa ibe yi-polyprotein eyodwa enkulu. Le polyprotein ibe isicutshungulwa yi-proteases yegciwane (noma ama-protease abambe iqhaza) ibe amaprotheni ahlelekile nangenasakhiwo. Ngakho-ke ama-protease egciwane ayizinhloso eziyinhloko zokwelapha, njengoba kubonakala ekwelapheni i-hepatitis C kanye ne-COVID-19.
4. Ukuphindaphindwa kwe-RNA: indima ye-RNA polymerase encike kwi-RNA
Isici esichaza kakhulu ama-virus e-RNA ukusebenzisa kwawo i-enzyme i-RNA-dependent RNA polymerase (RdRp), i-polymerase ekwazi ukukopisha i-RNA kusuka kuthempulethi ye-RNA. Amaseli abantu awanawo i-RdRp yokuphindaphinda kwe-RNA ye-cytoplasmic, ngakho-ke le enzyme cishe ihlala ibhalwa yigciwane futhi iyisisulu semithi ethile.
Inqubo yokuphindaphinda ivame ukwenzeka “ezimbonini zokuphindaphinda,” noma ezindaweni zolwelwesi ezivuselelwe kabusha ngamagciwane avela kuma-organelle eseli (isb., i-endoplasmic reticulum). Lezi zindawo zisiza ukugxila ezintweni zokuphindaphinda futhi zivikele i-RNA yegciwane ezinzwaneni zomzimba ezizalwa nazo.
Kuma-virus e-+RNA, i-RdRp iqala yenze umucu we-α-RNA njenge-intermediate, bese kusuka kule template ye-α-RNA, kwenziwa amakhophi amaningi amasha e-α-RNA. Kuma-virus e-α-RNA, i-RdRp kumele yenze umsebenzi wokubhala ngaphambi kokutheleleka ukuze ikhiqize i-mRNA. Ezimweni eziningi, i-RdRp isebenza ngokubambisana nama-cofactor afana nama-helicase (ukukhulula isakhiwo se-RNA) kanye nama-nucleotidyltransferases (ukwakheka kwe-cap noma ukuguqulwa kweziphetho ze-RNA).
5. Ukuguquka kwezakhi zofuzo, izinhlobo ezithile, kanye nokuziphendukela kwemvelo okusheshayo
I-RdRp ngokuvamile ayinawo amakhono okuhlola ukuhlolwa kwe-DNA polymerase, okuholela emazingeni aphezulu okuguquka kwamagciwane e-RNA. Lokhu kuphumela ekwandeni kwamagciwane akha "ama-quasispecies," iqoqo lezinhlobo ezihlobene eduze ngaphakathi kwe-host eyodwa. Le nzuzo yezinto eziphilayo ukuzivumelanisa ngokushesha nezingcindezi zokukhetha, njenge-antibodies, ukwelashwa ngamagciwane, noma umehluko ezindaweni zezicubu.
Kodwa-ke, amazinga aphezulu okuguquka kwezakhi zofuzo nawo abeka engcupheni "inhlekelele yamaphutha," ukuqongelela kokuguquka kwezakhi zofuzo okubangela ukuthi igciwane lilahlekelwe amandla okuphila. Amanye ama-antiviral asebenzisa lo mqondo ngokwandisa amaphutha okuphindaphinda. Ngokuthakazelisayo, ama-coronavirus ahlukile, ane-enzyme yokufunda kabusha (i-exoribonuclease) enciphisa izinga lokuguquka kwezakhi zofuzo uma kuqhathaniswa namanye amagciwane amaningi e-RNA, ewavumela ukuthi alondoloze ama-genome amakhulu.
6. Ukuvezwa kwezakhi zofuzo: ama-subgenomics, ukushintshashintsha uhlaka, kanye nokulawula
Ama-virus e-RNA asebenzisa amaqhinga ahlukahlukene ama-molecule ukuze andise ulwazi lwezakhi zofuzo ngaphakathi kwama-genome awo amancane. Isibonelo ukwakheka kwama-mRNA angaphansi kwe-genomic kuma-coronavirus, okuvumela ukuvezwa kwamaprotheni akhiwe avela ezindaweni ezithile ze-genome. Kukhona futhi nendlela yokushintsha i-ribosomal frameshifting, eshintsha uhlaka lokufunda ngesikhathi sokuhumusha ukuze i-RNA eyodwa ikhiqize amaprotheni amaningana ahlukene. Amanye amasu afaka phakathi ukumiswa kokufundwa kwe-codon kanye nokusetshenziswa kwama-promoter angaphakathi kuma-virus athile.
Ukulawulwa kokubonakaliswa kwezakhi zofuzo kuvame ukuhlotshaniswa nokulandelana kwe-RNA kanye nesakhiwo, kanye nokusebenzisana namaprotheni egciwane kanye nawabasingathi. Lezi zakhi zithonya lapho kukhiqizwa amaprotheni okuphindaphinda, lapho amaprotheni esakhiwo eba khona amakhulu, kanye nendlela igciwane eliphambukisa ngayo izinsiza zamaseli.
7. Ukuhlanganiswa nokukhululwa
Ngemva kokuba kukhiqizwe i-genome entsha kanye namaprotheni akhiwe, igciwane lihlanganisa inhlayiya entsha. Ukuhlanganiswa kuhilela ukupakisha i-RNA ku-capsid, evame ukuthembela ezimpawini zokupakisha ngaphakathi kwe-RNA. Amagciwane angamboziwe ngokuvamile aphuma nge-cell lysis, kuyilapho amagciwane amboziwe eqhuma nge-membrane yeseli noma i-organelle, esebenzisa ingxenye ye-membrane njenge-envelope. Inqubo yokuqhuma idinga ukuhlanganiswa kwamaprotheni e-matrix, ama-glycoprotein amboziwe, kanye nezinto zeseli.
8. Ukusebenzisana namasosha omzimba kanye namasu okugwema
I-RNA egciwane ibonwa yizinzwa zomzimba ezizalwa nazo njenge-RIG-I kanye ne-MDA5, ezithola i-RNA yangaphandle noma izakhiwo ezithile. Lokhu kutholwa kudala ukukhiqizwa kwe-interferon kanye nokusebenza kwezakhi zofuzo eziningi ezilwa namagciwane. Ukuze zisinde, amagciwane e-RNA athuthukisa amaprotheni alwa ne-interferon, afihle i-RNA yawo ngokuyivala kanye ne-methylation, noma afihle ukuphindaphindeka kwawo ngaphakathi kwezingxenye ze-membrane.
Le mpi yama-molecule inquma izinga lokutheleleka kanye nomphumela wokutheleleka. Ukuguquka okuncane kwamaprotheni amelene namasosha omzimba kungashintsha ikhono legciwane lokusabalala noma ukubangela izifo ezimbi kakhulu.
9. Imiphumela yokwelashwa, imijovo, kanye nokuxilonga
Ulwazi ngebhayoloji yama-molecule yamagciwane e-RNA luyisisekelo sokusungula izinto ezintsha kwezokwelapha. Ama-RdRp nama-protease e-viral ayizithako zemithi ezikhangayo ngoba abalulekile futhi aqondile. Ngasohlangothini lokugoma, ukuqonda amaprotheni angaphezulu kanye ne-mutational dynamics kubalulekile ekwakheni ama-antigen azinzile. Ukuxilongwa kwama-molecule njenge-RT-PCR kusebenzisa iqiniso lokuthi i-genome yegciwane iyi-RNA, okudinga isinyathelo sokuguqula i-RNA ibe yi-DNA ngaphambi kokukhulisa.
Ngaphezu kwalokho, ukuqapha izakhi zofuzo kusiza ukulandelela ukuvela kwamagciwane e-RNA nokuthola izinhlobo ezintsha. Lokhu kubaluleke kakhulu kumagciwane ashintsha ngokushesha noma asengozini yokuphinda ahlukaniswe.
Isiphetho
I-biology yama-molecule yamagciwane e-RNA ibonisa ukuthi izinto eziphilayo ezilula zingasebenzisa kanjani amasu okusinda ayinkimbinkimbi: ukungena emaseli, ukusebenzisa ama-ribosomes omuntu, ukukopisha ama-genome nge-RdRp, ukuguquka ngokushesha ngokuguqulwa kwezakhi zofuzo, nokugwema isimiso somzimba sokuzivikela. Ukuqonda kahle lezi zinqubo akubalulekile nje kuphela kwisayensi eyisisekelo ye-virology kodwa futhi kubeka isisekelo sokulawulwa kwezifo ngemigomo, imithi yokulwa namagciwane, kanye nobuchwepheshe besimanje bokuxilonga. Njengoba usongo olukhulayo lwezifo ezithathelwanayo lukhula, ukutadisha amagciwane e-RNA kuzoqhubeka nokuba yinsimu efanele futhi ekhula ngokushesha.
