tib neeg yuav tsis muaj nyob tsis muaj kab mob vim hais tias kab mob protein plays lub luag haujlwm tseem ceeb hauv kev loj hlob ntawm tib neeg lub embryo. Txawm li cas los xij, lub sijhawm, lawv ua rau muaj kev hem thawj nyob rau hauv daim ntawv ntawm cov kab mob xws li nyob rau hauv cov ntaub ntawv ntawm tus kab mob COVID-19 tam sim no. Ironically, kab mob suav nrog ~ 8% ntawm peb cov genome, uas tau txais thaum lub sijhawm evolution, ua rau peb "virtually a chimera".
Cov lus phem tshaj plaws thiab txaus ntshai tshaj plaws ntawm xyoo 2020 yam tsis muaj kev poob siab yog 'tus kab mob no'. Qhov tshiab mob hlwb yog lub luag haujlwm rau tus kab mob COVID-19 uas tsis tau pom dua tam sim no thiab yuav luag ze ntawm kev lag luam hauv ntiaj teb. Tag nrho cov no yog tshwm sim los ntawm ib tug me me particle uas tsis yog txawm xam tau tias yog 'tag nrho' nyob vim hais tias nws yog nyob rau hauv ib tug tsis ua hauj lwm lub xeev sab nraum tus tswv tsev, thaum tsuas perpetuating nyob rau hauv thaum kis tus tswv tsev. Ntau xav tsis thoob thiab poob siab yog qhov tseeb tias cov tib neeg tau nqa tus kab mob "genes" txij thaum lub sij hawm immemorial thiab tam sim no tus kab mob genes tsim ~ 8% ntawm tib neeg genome (1). Tsuas yog muab qhov no tso rau hauv kev pom, tsuas yog ~ 1% tib neeg genome yog lub luag haujlwm ua lub luag haujlwm ua cov protein uas txiav txim siab peb yog leej twg.
Zaj dab neeg ntawm kev sib raug zoo ntawm tib neeg thiab kab mob pib 20-100 lab xyoo dhau los thaum peb cov yawg koob tau kis los ntawm kab mob. Txhua tsev neeg endogenous retrovirus yog muab los ntawm ib qho kab mob ntawm cov kab mob germline los ntawm ib qho exogenous retrovirus uas tom qab kev koom ua ke rau hauv peb cov poj koob yawm txwv, nthuav thiab hloov zuj zus (2). Kev nthuav tawm ua raws li kev hloov pauv kab rov tav los ntawm niam txiv mus rau cov xeeb ntxwv thiab niaj hnub no peb muaj cov kab mob genomes embedded hauv peb DNA li. tib neeg endogenous retroviruses (HERVs). Qhov no yog cov txheej txheem txuas ntxiv thiab tej zaum yuav tshwm sim tam sim no. Nyob rau lub sijhawm ntawm evolution, cov HERVs tau txais kev hloov pauv, tau ua kom ruaj khov nyob rau hauv tib neeg genome thiab poob lawv lub peev xwm los ua tus kab mob. Cov endogenous retroviruses tsis tsuas yog tam sim no nyob rau hauv tib neeg tab sis muaj omnipresent nyob rau hauv tag nrho cov muaj sia nyob. Tag nrho cov kab mob endogenous retroviruses tau muab faib ua peb chav kawm (Class I, II thiab III) tshwm sim thoob plaws cov tsiaj sib txawv pom muaj kev sib raug zoo phylogenetic raws li lawv qhov sib xws (3) raws li tau piav qhia hauv daim duab hauv qab no. HERVs yog nyob rau pawg I.
Ntawm ntau yam embedded retroviruses muaj nyob rau hauv tib neeg genome, ib qho piv txwv classic tsim nyog hais txog ntawm no, yog ntawm cov protein retroviral uas yog lub hnab ntawv fusogenic siab heev hu ua syncytin, (5) uas nws lub luag haujlwm tseem ceeb hauv tus kab mob no yog fuse nrog cov cell ua kom muaj kab mob. Cov protein no tau tam sim no tau yoog rau hauv tib neeg tsim cov placenta (fusion ntawm cov hlwb los ua cov cell multinucleated) uas tsis yog tsuas yog muab zaub mov rau fetus los ntawm leej niam thaum cev xeeb tub tab sis kuj tseem tiv thaiv tus menyuam hauv plab los ntawm leej niam lub cev tiv thaiv kab mob vim yog lub cev tiv thaiv kab mob ntawm cov protein syncytin. Qhov tshwj xeeb HERV no tau ua pov thawj tias muaj txiaj ntsig zoo rau tib neeg haiv neeg los ntawm kev txhais nws lub neej.
HERVs kuj tau cuam tshuam los ntawm kev muab kev tiv thaiv hauv lub cev rau tus tswv tsev los ntawm kev tiv thaiv kab mob ntxiv los ntawm kev cuam tshuam kab mob los yog txo qhov mob hnyav ntawm tus kab mob thaum rov kis los ntawm hom zoo sib xws kab mob. Kev tshuaj xyuas xyoo 2016 los ntawm Katzourakis thiab Aswad (6) piav qhia txog qhov endogenous kab mob tuaj yeem ua raws li cov cai tswj hwm cov noob uas tswj kev tiv thaiv kab mob, yog li ua rau kev tiv thaiv kab mob. Nyob rau tib lub xyoo, Chuong et al (7) tau pom tias qee yam HERVs ua raws li kev tswj hwm kev txhim kho los ntawm kev hloov kho cov kev qhia ntawm IFN (interferon) inducible genes li no muab kev tiv thaiv innate. HERV cov khoom lag luam tuaj yeem ua raws li cov kab mob sib txuas nrog cov qauv molecular (PAMPs), ua rau cov cellular receptors lub luag haujlwm rau tus tswv thawj kab ntawm kev tiv thaiv (8-10).
Lwm qhov nthuav dav ntawm HERVs yog tias qee qhov ntawm lawv pom muaj cov kab mob sib kis, piv txwv li cov ntawv luam sib txawv muaj nyob rau hauv genome vim muaj cov xwm txheej ntxiv. Kev tshawb fawb ntawm 20 yam uas muaj nyob rau hauv cov haiv neeg sib txawv tau nthuav tawm cov qauv sib txawv ntawm 0-87% hauv txhua yam kev kawm (11). Qhov no tuaj yeem muaj feem cuam tshuam rau kev ua cov kab mob los ntawm kev ua kom muaj qee cov noob uas tsis nyob twj ywm.
Qee qhov HERVs kuj tau pom tias muaj feem cuam tshuam nrog kev txhim kho ntawm cov kab mob autoimmune xws li ntau yam sclerosis (12). Raws li ib txwm muaj lub cev nqaij daim tawv, HERV qhia tau nruj nruj thaum nyob rau hauv cov kab mob pathological vim muaj kev hloov pauv ntawm sab nraud / sab hauv ib puag ncig, kev hloov pauv hormonal thiab / lossis microbial kev sib cuam tshuam tuaj yeem ua rau tsis zoo ntawm HERV qhia, ua rau muaj kab mob.
Cov yam ntxwv saum toj no ntawm HERVs qhia tias tsis yog lawv nyob hauv tib neeg genome yog qhov kev zam tsis tau tab sis lawv muaj peev xwm tswj hwm homeostasis ntawm lub cev tiv thaiv kab mob los ntawm kev ua kom los yog ua rau nws, yog li ua rau muaj kev cuam tshuam sib txawv (los ntawm kev muaj txiaj ntsig ua rau muaj kab mob) hauv cov tswv.
Tus kab mob COVID-19 tseem tshwm sim los ntawm tus kab mob retrovirus SARS-nCoV-2, uas yog nyob rau tsev neeg mob khaub thuas, thiab nws tuaj yeem pom tau tias, thaum lub sijhawm hloov pauv, genomes ntsig txog tsev neeg ntawm no. kab mob tau integrated rau hauv tib neeg genome thiab tam sim no tam sim no ua HERVs. Nws yog surmised tias cov HERVs no yuav nthuav tawm ntau yam polymorphisms, raws li tau hais los saum no, ntawm cov neeg ntawm ntau haiv neeg. Cov polymorphisms no tuaj yeem yog nyob rau hauv daim ntawv sib txawv ntawm tus lej ntawm HERVs no thiab / lossis muaj lossis tsis muaj kev hloov pauv (hloov hauv cov kab ke genome) sau ntau lub sijhawm. Qhov kev sib txawv no hauv HERVs sib xyaw ua ke tuaj yeem muab lus piav qhia rau qhov sib txawv ntawm cov neeg tuag thiab qhov hnyav ntawm COVID-19 kab mob hauv ntau lub teb chaws cuam tshuam los ntawm kev sib kis.
***
References:
1. Griffiths DJ 2001. Endogenous retroviruses nyob rau hauv lub tib neeg genome kab zauv. Genome Bio. (2001); 2(6) Xyuas 1017. DOI: https://doi.org/10.1186/gb-2001-2-6-reviews1017
2. Boeke, JD; Stoye, JP (1997). "Retrotransposons, Endogenous Retroviruses, thiab Evolution ntawm Retroelements". Hauv Coffin, JM; Hughes, SH; Varmus, HE (eds.). Retroviruses. Cold Spring Harbor Laboratory Press. PMID 21433351.
3. Vargiu L, et al. Classification thiab characterization ntawm tib neeg endogenous retroviruses; mosaic cov ntaub ntawv muaj ntau. Retrovirology (2016); 13:7 KWB: https://doi.org/10.1186/s12977-015-0232-y
4. Classes_of_ERVs.jpg: Jern P, Sperber GO, Blomberg J (derivative work: Fgrammen (talk)), 2010. Available online at https://commons.wikimedia.org/wiki/File:Classes_of_ERVs.svg Tau txais los ntawm 07 May 2020
5. Ntshav, JL; Lavillette, D; Cheynet, V; Boton, O; Oriol, G; Chapel-Fernandes, S; Mandrandes, S; Mallet, F; Cosset, FL (7 Plaub Hlis 2000). "Lub hnab ntawv glycoprotein ntawm cov tib neeg endogenous retrovirus HERV-W yog qhia nyob rau hauv tib neeg placenta thiab fuses hlwb qhia hom D mammalian retrovirus receptor ". J. Virol. 74 (7): 3321–9. DOI: https://doi.org/10.1128/jvi.74.7.3321-3329.2000.
6. Katzourakis A, thiab Aswad A. Evolution: Endogenous kab mob Muab Shortcuts hauv Antiviral Immunity. Tam sim no Biology (2016). 26: R427-R429. http://dx.doi.org/10.1016/j.cub.2016.03.072
7. Chuong EB, Elde NC, thiab Feschotte C. Regulatory evolution of innate immunity by co-option of endogenous retroviruses. Science (2016) Vol. 351, Is Taws Nem 6277, pp. 1083-1087. DOI: https://doi.org/10.1126/science.aad5497
8. Wolff F, Leisch M, Greil R, Risch A, Pleyer L. Ob-edged ntaj ntawm (re) nthuav tawm cov noob los ntawm cov tshuaj hypomethylating: los ntawm cov kab mob mimicry mus rau exploitation raws li priming agents rau lub hom phiaj tiv thaiv kab mob checkpoint modulation. Cell Commun Signal (2017) 15:13. DOI: https://doi.org/10.1186/s12964-017-0168-z
9. Hurst TP, Magiorkinis G. Ua kom lub cev tiv thaiv kab mob hauv lub cev los ntawm endogenous retroviruses. J Gen Virol. (2015) 96:1207–1218. DOI: https://doi.org/10.1099/vir.0.000017
10. Chiappinelli KB, Strissel PL, Desrichard A, Chan TA, Baylin SB, Correspondence S. Inhibiting DNA methylation ua rau interferon teb nyob rau hauv mob qog noj ntshav ntawm dsRNA nrog rau endogenous retroviruses. Cell (2015) 162:974–986. DOI: https://doi.org/10.1016/j.cell.2015.07.011
11. Mehrab G, Sibel Y, Kaniye S, Sevgi M thiab Nermin G. Human endogenous retrovirus-H insertion kev tshuaj ntsuam. Molecular Medicine Reports (2013). DOI: https://doi.org/10.3892/mmr.2013.1295
12. Gröger V, thiab Cynis H. Tib neeg Endogenous Retroviruses thiab lawv lub luag haujlwm hauv kev txhim kho cov kab mob autoimmune xws li Ntau yam Sclerosis. Pem hauv ntej Microbiol. (2018); 9: 265 IB: https://doi.org/10.3389/fmicb.2018.00265
***
