Biology ya Ma Molecular ya Mavairasi a RNA
Ma RNA virus ndi gulu la ma virus omwe majini awo amakhala ndi ribonucleic acid (RNA). Gululi limaphatikizapo tizilombo toyambitsa matenda tofunika kwambiri mwa anthu, nyama, ndi zomera, monga fuluwenza, dengue, hepatitis C, polio, chiwewe, chikuku, ndi SARS-CoV-2. Kupadera kwa ma RNA virus kuli mu njira zawo zoberekera, kuchuluka kwa kusintha kwa majini, ndi njira zopewera chitetezo cha mthupi. Kumvetsetsa za biology ya ma RNA virus ndikofunikira kwambiri pakupanga katemera, mankhwala oletsa mavairasi, ndi njira zodziwira matenda.
1. Kapangidwe ka majini ndi kapangidwe ka mavairasi a RNA
Kawirikawiri, majini a kachilombo ka RNA amatha kukhala ndi chingwe chimodzi (ssRNA) kapena awiri (dsRNA). Mu ssRNA, majini amatha kukhala ndi positive-sense (+RNA) kapena negative-sense (−RNA). Ma virus a +RNA ali ndi majini omwe amatha kugwira ntchito mwachindunji ngati mRNA, kotero amasinthidwa nthawi yomweyo ndi ribosomes ya selo lolandira pambuyo polowa mu cytoplasm. Zitsanzo zikuphatikizapo Picornaviridae (monga poliovirus) ndi Flaviviridae (monga dengue). Mosiyana ndi zimenezi, ma virus a −RNA (monga fuluwenza ndi chiwewe) amakhala ndi majini ogwirizana ndi mRNA, kotero ayenera choyamba kusinthidwa kukhala mRNA ndi ma enzymes a kachilombo asanamasuliridwe.
Ma genome a kachilombo ka RNA amathanso kugawidwa m'magawo kapena osagawidwa m'magawo. Fuluwenza ili ndi genome yogawidwa m'magawo, yomwe imalola "kusinthananso," kusinthana kwa magawo pakati pa mavairasi akamakhudza selo lomwelo. Chochitikachi chingapange mitundu yatsopano yomwe ingayambitse kufalikira kwakukulu. Pakadali pano, mavairasi ambiri a RNA ali ndi genome imodzi, yayitali yomwe nthawi zambiri imakhala ndi polyprotein, yomwe imagawika kukhala mapuloteni ogwira ntchito.
Kuwonjezera pa ma protein-coding sequences (ma open reading frames/ORFs), ma RNA viral genomes ali ndi zinthu zosalemba ma code kumapeto kwa 5' ndi 3' zomwe ndizofunikira kuti RNA ibwerezedwe, imasuliridwe, komanso ikhale yokhazikika. Kapangidwe kachiwiri monga hairpins ndi pseudoknots nthawi zambiri zimawonetsa kumangirirana kwa mapuloteni a viral ndi zinthu zomwe zimapangitsa maselo kukhala ofunikira.
2. Kulowa kwa kachilomboka ndi kutulutsidwa kwa majini (kutsegula chivundikiro)
Moyo wa kachilombo ka RNA umayamba pamene kamalumikizana ndi cholandirira pamwamba pa selo la wolandira. Kuyanjana kumeneku kumatsimikizira kukwera kwa minofu ndi kudziwika kwa wolandira. Pambuyo polumikizana, kachilomboka kamalowa kudzera mu endocytosis kapena membrane fusion. Mavairasi ozungulira, monga chimfine ndi coronaviruses, nthawi zambiri amagwiritsa ntchito membrane fusion, pomwe mavairasi ambiri omwe sanalowemo amalowa kudzera mu endocytosis kenako amasinthidwa mawonekedwe kuti atulutse capsid yawo.
Kutsegula chivundikiro—kutulutsa genome ya RNA kuchokera ku capsid—ndi sitepe yofunika kwambiri. Ngati RNA sinatulutsidwe pamalo oyenera komanso panthawi yoyenera, kubwerezabwereza sikudzachitika. Mu ma virus ena, pH yotsika mu endosome imayambitsa kusintha kwa kapangidwe ka mapuloteni a ma virus, zomwe zimapangitsa kuti genome ithawire mu cytoplasm.
3. Kumasulira: momwe mavairasi amagwiritsira ntchito ma ribosome a anthu
Popeza mavairasi alibe ma ribosome, amadalira makina omasulira a selo lokhalamo. Mavairasi a RNA amatha kumasuliridwa mwachindunji, koma ayenera kuthana ndi zopinga zingapo: mpikisano ndi mRNA ya selo, kufunikira kwa "chipewa" kumapeto kwa 5', ndi njira zowongolera khalidwe la selo.
Mavairasi ena ali ndi malekezero a 5' monga mRNA ya host (monga ma coronaviruses), pomwe ena amagwiritsa ntchito njira zina, monga internal ribosome entry site (IRES) mu ma picornaviruses, zomwe zimathandiza ribosome kuyambitsa kumasulira popanda kapu. Mavairasi, monga chimfine, amagwiritsanso ntchito "kuthyola kapu," kuba kapu kuchokera ku host mRNA kuti agwiritse ntchito pa mavairasi awo a mRNA. Njira izi ndizofunikira mu biology ya mavairasi a RNA, chifukwa ndi omwe angawonongedwe ndi mankhwala oletsa mavairasi.
Mu ma virus ambiri a RNA, genome imasandulika kukhala polyprotein imodzi yayikulu. Polyprotein iyi imakonzedwa ndi ma virus protease (kapena ma receptor protease) kukhala mapuloteni omangira komanso osakhala a structural. Chifukwa chake ma virus protease ndi omwe amafunikira kwambiri pochiza, monga momwe zimaonekera pochiza matenda a chiwindi C ndi COVID-19.
4. Kubwerezabwereza kwa RNA: ntchito ya RNA polymerase yodalira RNA
Chizindikiro chachikulu cha ma RNA virus ndi kugwiritsa ntchito enzyme ya RNA-dependent RNA polymerase (RdRp), polymerase yomwe imatha kukopera RNA kuchokera ku template ya RNA. Maselo a anthu alibe RdRp yopangira cytoplasmic RNA replication, kotero enzyme iyi nthawi zambiri imasungidwa ndi kachilombo ndipo ndi cholinga chapadera cha mankhwala.
Njira yobwerezabwereza nthawi zambiri imachitika mu "mafakitale obwerezabwereza," kapena magawo a nembanemba omwe amasinthidwanso ndi mavairasi ochokera ku ma cell organelles (monga, endoplasmic reticulum). Magawo awa amathandiza kuyika zinthu zobwerezabwereza ndikuteteza ma RNA a mavairasi ku masensa oteteza chitetezo chamthupi.
Pa ma virus a +RNA, RdRp imapanga chingwe cha α-RNA ngati cholumikizira, kenako kuchokera pa template iyi ya α-RNA, makope ambiri atsopano a α-RNA amapangidwa. Pa ma virus a α-RNA, RdRp iyenera kuchita ntchito yolemba ma transcription kumayambiriro kwa matendawa kuti ipange mRNA. Nthawi zambiri, RdRp imagwira ntchito limodzi ndi zinthu monga ma helicase (kutsegula kapangidwe ka RNA) ndi ma nucleotidyltransferases (kupanga kapu kapena kusintha malekezero a RNA).
5. Kusintha kwa zinthu, mtundu wa zinthu, ndi kusintha kwachangu
RdRp nthawi zambiri imakhala ndi mphamvu zowerengera DNA polymerase, zomwe zimapangitsa kuti ma RNA virus akhale ndi ma virus ambiri. Izi zimapangitsa kuti ma virus akhale ndi ma quasispecies, omwe ndi mitundu yosiyanasiyana yofanana mkati mwa munthu m'modzi. Ubwino wachilengedwewu ndikusintha mwachangu ku zovuta zosankhidwa, monga ma antibodies, ma antiviral therapy, kapena kusiyana kwa malo okhala minofu.
Komabe, kuchuluka kwa kusintha kwa maselo kumaika pachiwopsezo "cholakwika chachikulu," kusonkhanitsa kwa kusintha kwa maselo komwe kumapangitsa kuti kachilomboka katayike. Mankhwala ena oletsa mavairasi amagwiritsa ntchito lingaliroli powonjezera zolakwika zobwerezabwereza. Chochititsa chidwi n'chakuti, ma coronavirus ndi osiyana, ali ndi enzyme yowerengera (exoribonuclease) yomwe imachepetsa kuchuluka kwa kusintha kwa maselo poyerekeza ndi ma virus ena ambiri a RNA, zomwe zimawalola kusunga majini akuluakulu.
6. Kufotokozera majini: subgenomics, frameshifting, ndi regulation
Ma virus a RNA amagwiritsa ntchito njira zosiyanasiyana zopezera ma molekyulu kuti awonjezere chidziwitso cha majini mkati mwa majini awo ang'onoang'ono. Chitsanzo ndi kupanga ma mRNA a subgenomic mu ma coronavirus, omwe amalola kufotokozera mapuloteni opangidwa kuchokera kumadera enaake a majini. Palinso njira yosinthira ma ribosomal frame, yomwe imasintha chimango chowerengera panthawi yomasulira kuti RNA imodzi ipange mapuloteni osiyanasiyana. Njira zina zimaphatikizapo kuyimitsa kuwerenga kwa codon ndi kugwiritsa ntchito zolimbikitsira zamkati mwa ma virus ena.
Kulamulira kagwiritsidwe ntchito ka majini nthawi zambiri kumalumikizidwa ndi kachitidwe ka RNA, komanso kuyanjana ndi mapuloteni a mavairasi ndi omwe ali m'thupi. Zinthu zimenezi zimakhudza nthawi yomwe mapuloteni obwerezabwereza amapangidwa, nthawi yomwe mapuloteni opangidwa amakhala amphamvu, komanso momwe kachilomboka kamasinthira zinthu zamaselo.
7. Kumanga ndi kumasula
Pambuyo poti majini atsopano ndi mapuloteni opangidwa, kachilomboka kamasonkhanitsa tinthu tatsopano. Kumanga kumaphatikizapo kuyika RNA mu capsid, yomwe nthawi zambiri imadalira zizindikiro zoyika mkati mwa RNA. Mavairasi osatsekedwa nthawi zambiri amatuluka kudzera mu cell lysis, pomwe mavairasi otsekedwa amatuluka kudzera mu cell membrane kapena organelle, pogwiritsa ntchito gawo la nembanemba ngati envelopu. Njira yophukira imafuna kugwirizana kwa mapuloteni a matrix, envelopu glycoproteins, ndi zinthu zamaselo.
8. Kuyanjana ndi chitetezo cha mthupi ndi njira zopewera
RNA ya mavairasi imadziwika ndi masensa obadwa nawo a chitetezo chamthupi monga RIG-I ndi MDA5, omwe amazindikira RNA yachilendo kapena kapangidwe kake. Kuzindikira kumeneku kumayambitsa kupanga interferon ndi kuyambitsa majini ambiri oletsa mavairasi. Kuti apulumuke, mavairasi a RNA amapanga mapuloteni otsutsana ndi interferon, kubisa RNA yawo kudzera mu chivindikiro ndi methylation, kapena kubisa kubwerezabwereza kwawo mkati mwa zigawo za nembanemba.
Nkhondo ya mamolekyu iyi imatsimikizira kuchuluka kwa matenda ndi zotsatira za matenda. Kusintha pang'ono kwa mapuloteni otsutsana ndi chitetezo cha mthupi kumatha kusintha kuthekera kwa kachilomboka kufalikira kapena kuyambitsa matenda oopsa kwambiri.
9. Zotsatira zake pa mankhwala, katemera, ndi matenda
Kudziwa za biology ya ma RNA virus ndi maziko a luso la zamankhwala. RdRp ndi ma virus protease ndi mankhwala okongola chifukwa ndi ofunikira komanso odziwika bwino. Kumbali ya katemera, kumvetsetsa mapuloteni apamwamba ndi kusintha kwa majini ndikofunikira kwambiri popanga ma antigen okhazikika. Kuzindikira ma molecule monga RT-PCR kumagwiritsa ntchito mfundo yakuti majini a kachilombo ndi RNA, zomwe zimapangitsa kuti pakhale njira yosinthira ma RNA kukhala DNA isanakulitsidwe.
Kuphatikiza apo, kuyang'anira majini kumathandiza kutsatira kusintha kwa mavairasi a RNA ndikupeza mitundu yatsopano. Izi ndizofunikira makamaka kwa mavairasi omwe amasintha mwachangu kapena omwe ali pachiwopsezo chobwereranso.
Mapeto
Sayansi ya ma virus a RNA ikuwonetsa momwe zamoyo zosavuta zingagwiritsire ntchito njira zovuta zopulumukira: kulowa m'maselo, kugwiritsa ntchito ma ribosome a anthu, kukopera majini kudzera mu RdRp, kusintha mwachangu kudzera mu kusintha kwa majini, ndikupewa chitetezo chamthupi. Kumvetsetsa bwino njirazi sikuti ndikofunikira kokha pa sayansi yoyambira ya virology komanso kumayala maziko owongolera matenda kudzera mu katemera, mankhwala oletsa mavairasi, ndi ukadaulo wamakono wozindikira matenda. Ndi chiwopsezo chowonjezeka cha matenda opatsirana, kuphunzira ma virus a RNA kupitilira kukhala gawo lofunikira komanso lokukula mwachangu.
