(Open access funding provided by Semmelweis University)
(Semmelweis University Start-up Grant (No. 11725))
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 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.
