SARS-CoV-2 infection in HIV-infected patients: potential role in the high mutational load of the Omicron variant emerging in South Africa

GeroScience - Tập 44 Số 5 - Trang 2337-2345 - 2022
Katalin Réka Tarcsai1, Oliga Corolciuc1, Attila Tordai2, J Ongrádi2
1Doctoral School, Semmelweis University, Budapest, Hungary
2Department of Transfusion Medicine, Semmelweis University, Nagyvárad tér 4, Budapest, 1089, Hungary

Tóm tắt

AbstractA new variant of SARS-CoV-2 named Omicron (B.1.1.529) was isolated from an HIV-infected patient in Botswana, South Africa, in November 2021. Whole genome sequencing revealed a multitude of mutations and its relationship to the mutation-rich Alpha variant that had been isolated from a cancer patient. It is conceivable that very high prevalence of HIV-infected individuals as susceptible hosts in South Africa and their immunocompromised state may predispose for accumulation of coronavirus mutations. Coronaviruses uniquely code for an N-terminal 3′ to 5′exonuclease (ExoN, nsp14) that removes mismatched nucleotides paired by the RNA dependent RNA polymerase. Its activity depends preferably on Mg2+ and other divalent cations (manganese, cobalt and zinc). On the contrary, methyl transferase activity of non-structural protein (nsp) 14 and nsp16 both complexed with nsp10 requires Mn2+. Enzymes in successive stages of HIV infections require the same cations. In HIV-infected organisms, a subsequent coronavirus infection encounters with altered homeostasis of the body including relative starvation of divalent cations induced by interleukin production of HIV-infected cells. It is hypothesized that selective diminished efficacy of ExoN in the absence of sufficient amount of magnesium may result in the accumulation of mutations. Unusual mutations and recombinations of heterologous viruses detected in AIDS patients also suggest that long-lasting persistence of superinfecting viruses may also contribute to the selection of genetic variants. Non-nucleoside reverse transcriptase inhibitors partially restore divalent cations’ equilibrium. As a practical approach, implementation of highly active antiretroviral therapy against HIV replication and vaccination against coronaviruses may be a successful strategy to reduce the risk of selection of similar mutants.

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Tài liệu tham khảo

Kandeel M, Mohamed MEM, El-Lateef HMA, Verugopala KN, El-Beltagi HS. Omicron variant genome evolution and phylogenetics. J Med Virol. 2021;94:1627–32. https://doi.org/10.1002/jmv.27515.

Chen J, Wei G-W. Omicron BA.2 (B.1.1.529.2): high potential to becoming the next dominating variant. J Phys Chem Lett. 2022;13:3840–9. https://doi.org/10.1021/acs.jpclett.2c00469.

He X, Hong W, Pan X, Lu G, Wei X. SARS-CoV-2 Omicron variant: characteristics and prevention. Med Comm. 2021;2:838–45. https://doi.org/10.1002/mco2.110.

Karim SSA, Karim QA. Omicron SARS-CoV-2 variant: a new chapter in the COVID-19 pandemic. Lancet. 2021;398:2126–8. https://doi.org/10.1016/S0140-6736(21)02758-6.

Desingu PA, Nagarajan K, Kuldeep D. Emergence of omicron third lineage BA.3 and its importance. J Med Virol. 2022;94:1808–10. https://doi.org/10.1002/jmv.27601.

Grehan K. Molecular virology of SARS-CoV-2. Microbiol Today. 2021:66–9. www.microbiologysociety.org/COVID19hub.

Wise J. COVID-19: New coronavirus variant is identified in UK. Br Med J. 2020;371:m4857. https://doi.org/10.1136/bmj.m4857.

Akullian A, Vandormael A, iller JCV, Bersteyn A, Wenger E, Cuadros D, Gareta D, Barminghausen T, Herbst K, Tanser F. Large age shifts in HIV uncidence pattern in KwaZulu-Natal, South Africa. PNAS. 2021;118:e2013164118. https://doi.org/10.1073/pnas-2013164118.

Boulle A, Davis MA, Hussey H, Western Cape Government Health coworkers. Risk factors for COVID-19 death in a population cohort study from the Western Cape Province, South Africa. Clin Infect Dis. 2021;73:e2005-15. https://doi.org/10.1093/cid/ciaa1198.

Barbera LK, Kamis KF, Rowan SE, Davis AJ, Shehata S, Carlson JJ, Johnson SC, Erlandson KM. HIV and COVID-19: review of clinical course and outcomes. HIV Res Clin Pract. 2021;22:102–18. https://doi.org/10.1080/25787489.2021.1975608.

Ongrádi J, Kövesdi V. Factors that may impact on immunosenescence: an appraisal. Immun Ageing. 2010;7:7. https://doi.org/10.1186/1742-49.33.7.7.

Dalzini A, Petrara MR, Ballin GZ, Zanchetta M, Giacinto C, De Rossi A. Biological aging and immune senescence in children with perinatally acquired HIV. Immunol Res 2020;16:8641616. eCollection2020. https://doi.org/10.1155/2020/8641616

Minasov G, Rosas-Lemus M, Shuvalova L, Inniss NL, Brunzell JS, Daczkowski CM, Hoover P, Mesecar AD, Satchell KJF. Mn2+ coordinates Cap-0-RNA to align substrates for efficient 2’-O-methyl transfer by SARS-CoV-2 nsp16. Sci Signal. 2021;14:eabh2071. https://doi.org/10.1126/scisignal-abh2071.

Bouvet M, Debarnot C, Imbert I, Selisko B, Snijder EJ, Canard B, Decroly E. In vitro reconstruction of SARS-Coronavirus mRNA Cap methylation. PLos Pathog. 2010;6:e1000863. https://doi.org/10.1371/journal.ppat.1000863.

Bouvet M, Imbert I, Subissi L, Gluais L, Canard B, Decroly E. RNA 3’-end mismatch excision by the severe acute respiratory syndrome coronavirus nonstructural protein nsp10/nsp14 exoribonuclease complex. PNAS. 2012;109:9372–7. https://doi.org/10.1073/pnas.1201130109.

Tahir M. Coronavirus genomic nsp14-ExoN structure, role, mechanism, and potential application as a drug target. J Med Virol. 2021;93:4258–64. https://doi.org/10.1002/jmv.27009.

Robson F, Khan KS, Le TK, Paris C, Demirbag S, Barfuss P, Rocchi P, Ng W-L. Coronavirus RNA proofreading: molecular basis and therapeutic targeting. Mol Cell. 2020;79:710–27. https://doi.org/10.1016/j.molcel.2020.07.027.

Hikmet F, Méar L, Edvinnson A, Micke P, Uhlén M, Lindskog C. The protein expression profile of ACE2 in human tissues. Mol Syst Biol. 2020;16:e9610. https://doi.org/10.15252/20209610.

Khan N, Chen X, Geiger JD. Role of divalent cations in HIV-1: replication and pathogenicity. Viruses. 2020;12:471. https://doi.org/10.3390/V.12040471.

Chaigne-Delalande B, Lenardo MJ. Divalent cation signaling in immune cells. Trends Immunol. 2014;3:332–44. https://doi.org/10.1016/j.it.2014.05.001.

Achuthan V, Singh K, DeStefano JJ. Physiological Mg2+ conditions significantly alter the inhibition of HIV-1 and HIV-2 reverese transcripase by nucleoside and non-nucleoside inhibitors in vitro. Biochemistry. 2017;56:33–46. https://doi.org/10.1021/acs.biochem.6b00943.

De Stefano JJ. Non-nucleoside reverse transcriptase inhibitors inhibit reverse transcriptase through a mutually exclusive interaction with divalent cation-dNTP complexes. Biochemistry. 2019;58:2176-2187-. https://doi.org/10.1021/acs.biochem.9b00028.

Jones CYY, Tang AM, Forester JH, Huang J, Hendricks KM, Knox TA, Spiegelman D, Semba RD, Woods MN. Micronutrient levels and HIV diseases status in HIV-infected patients on highly active antiretroviral therapy in the Nutrition for Healthy Living Cohort. J Acquir Immune Defic Syndr. 2006;43:475–82. https://doi.org/10.1097/01.qai.000243096.27029.fe.

Sigfried N, Irham JH, Visser ME, Rollins NN. Micronutrient supplementation in pregnant women with HIV-infection. Cochrane Database Syst Rev. 2012;3:CD009775. https://doi.org/10.1002/14651858.CD009755.

Ongrádi J, Stercz B, Kövesdi V, Nagy K, Pistello M. Interaction of FIV with heterologous microbes in the feline AIDS model. In: Saxena KS (ed). Curr Perspect HIV Infect Intech, Rijeka, Croatia, 2013, 447–69. https://doi.org/10.5772/52767.

Thompson BJ, Efstathiou S, Honess RW. Acquisition of the human adeno-associated virus type 2 rep gene by human herpesvirus type 6. Nat Cell Biol. 1991;351:78–80. https://doi.org/10.1038/351078a0.

Araujo JC, Doniger J, Kashanchi F, Hermonat PL, Thompson J, Rosenthal LJ. Human herpesvirus 6A ts suppresses both transformation by H-ras and transcription by H-ras and human immunodeficiency virus type 1 promoters. J Virol. 1995;69:4933–40. https://doi.org/10.1128/JVI.69.8.4933-4940.1995.

Ongrádi J, Cunningham C, Szilágyi JF. The role of polypeptides L and NS in the transcription process of vesicular stomatitis virus New Jersey using the temperature sensitive mutant E1. J Gen Virol. 1985;66:1011–23. https://doi.org/10.1099/0022-1317-66-5-1011.

Hierholzer JC. Adenoviruses in the immunocmpromised host. Clin Microbiol Rev. 1992;5:262–74. https://doi.org/10.1128/CMR.5.3.262.

Bacon TH, Levin MJ, Leary JJ, Sarisky RT, Sutton D. Herpes simplex virus resistance to acyclovir and penciclovir after two decades of antiviral therapy. Clin Microbiol Rev. 2003;16:114–28. https://doi.org/10.1128/CMR.16.1.114-128.2003.

Bush LM, Talledo-Thais K, Casal-Fernandez A, Perez MT. Resistant herpes simplex infection and HIV: A potential diagnostic and therapeutic dilemma. Lab Med. 2011;42:452–7. https://doi.org/10.1309/LMMVWC1EX7AW8ZMD.

Phan T, Boes S, McCullough M, Gribschaw J, Marsh JW, Harrison LH, Wells A. First detection of SARS-CoV-2 Omicron BA.4 variant in Western Pennsylvania, United States. J Med Virol. 2022. https://doi.org/10.1002/jmv.27846.

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