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bioRxiv · 10.1101/2022.10.24.513636

In vitro replicative potential of an HIV-1/MO intergroup recombinant virus compared to HIV-1/M and HIV-1/O parental viruses

Moisan, A.·De Oliveira, F.·Vautrin, M.·Alessandri-Gradt, E.·Mourez, T.·Plantier, J.-C.
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Abstract

HIV-1 is characterized by high genetic diversity and genetic recombination is one of the major evolution processes. Despite their great genetic divergence, HIV-1 group M, pandemic, and group O, endemic in Cameroon, can generate HIV-1/MO intergroup recombinants. The current description of 19 HIV-1/MO recombinant forms (URF_MO) raises the question of a possible benefit of the recombination and the modalities of their emergence. Therefore, the objectives of this work were to study in vitro the replicative potential of HIV-1/MO recombinant forms. The replicative potential was analyzed, based on a simple recombination pattern, [Ogag/pol-Menv], harboring a breakpoint in Vpr, due to a recombination hotspot in this region. For this, a chimeric infectious molecular clone (IMC) was synthesized from HIV-1/M subtype B and HIV-1/O subgroup T and recombinant viruses were obtained by transfection and co-culture. To compare the replicative potential of recombinant viruses with HIV-1/M and HIV-1/O parental viruses, two markers were monitored in culture supernatants: Reverse Transcriptase (RT) activity and P24 antigen concentration. The results showed a superiority of the group M parental virus compared to group O for both markers. In contrast, for the HIV-1/OM recombinant virus, RT activity data did not overlap with the concentration of P24 antigen, suggesting a hybrid behavior of the recombinant, in terms of enzyme activity and P24 production. These results highlighted many hypotheses about the impact of recombination on replicative potential and demonstrated once again the significant plasticity of HIV genomes and their infinite possibility of evolution. ImportanceHIV-1/M and HIV-1/O can generate HIV-1/MO intergroup recombinants. The current description of 19 URF_MO raises the question of a possible benefit of recombination in terms of emergence. The objectives of this work were to study in vitro the replicative potential of HIV-1/MO recombinant viruses. For this, a chimeric infectious molecular clone (IMC) generated from HIV-1/M subtype B and HIV-1/O subgroup T and recombinant viruses were obtained by transfection and co-culture. To compare the replicative potential of recombinant viruses with HIV-1/M and HIV-1/O parental viruses, RT activity and P24 antigen concentration were monitored in culture supernatants. A superiority of the group M parental virus compared to group O was observed for both markers whereas a hybrid behavior in terms of enzyme activity and P24 production was found for the recombinant virus. These results demonstrated once again the significant plasticity of HIV genomes and their infinite possibility of evolution.

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Moisan, A., De Oliveira, F., Vautrin, M., Alessandri-Gradt, E., Mourez, T., Plantier, J.-C.. 2022-10-25. In vitro replicative potential of an HIV-1/MO intergroup recombinant virus compared to HIV-1/M and HIV-1/O parental viruses. https://doi.org/10.1101/2022.10.24.513636

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