tetano
Editor, Senior Moderator
Geroscience
. 2022 Jun 24.
doi: 10.1007/s11357-022-00603-6. Online ahead of print.
SARS-CoV-2 infection in HIV-infected patients: potential role in the high mutational load of the Omicron variant emerging in South Africa
Katalin Réka Tarcsai[SUP] #[/SUP][SUP] 1 [/SUP], Oliga Corolciuc[SUP] #[/SUP][SUP] 1 2 [/SUP], Attila Tordai[SUP] 2 [/SUP], József Ongrádi[SUP] 3 4 [/SUP]
Affiliations
Abstract
A 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 Mg[SUP]2+[/SUP] 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 Mn[SUP]2+[/SUP]. 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.
Keywords: Coronavirus; Divalent cations; Exonuclease; Human immunodeficiency virus; Interaction; Variant Omicron.
. 2022 Jun 24.
doi: 10.1007/s11357-022-00603-6. Online ahead of print.
SARS-CoV-2 infection in HIV-infected patients: potential role in the high mutational load of the Omicron variant emerging in South Africa
Katalin Réka Tarcsai[SUP] #[/SUP][SUP] 1 [/SUP], Oliga Corolciuc[SUP] #[/SUP][SUP] 1 2 [/SUP], Attila Tordai[SUP] 2 [/SUP], József Ongrádi[SUP] 3 4 [/SUP]
Affiliations
- PMID: 35739343
- DOI: 10.1007/s11357-022-00603-6
Abstract
A 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 Mg[SUP]2+[/SUP] 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 Mn[SUP]2+[/SUP]. 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.
Keywords: Coronavirus; Divalent cations; Exonuclease; Human immunodeficiency virus; Interaction; Variant Omicron.