Similarities between HIV-1 and HCV genetic and phenotypic protease quasispecies diversity


J. Virol. doi:10.1128/JVI.01097-1


Human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) are two highly variable RNA viruses that cause chronic infections in humans. Although HCV likely preceded the AIDS epidemic by some decades, the global spread of both viruses is a relatively recent event. Nevertheless, HCV global diversity is higher than that of HIV-1. To identify differences in mutant diversity, we compared the HIV-1 protease and HCV NS3 protease quasispecies. Three protease gene quasispecies samples per virus, isolated from a total of six infected patients, were genetically and phenotypically analyzed at high resolution (HIV-1, 308 individual clones; HCV, 299). Single nucleotide variant frequency did not differ between quasispecies from the two viruses (HIV-1, 2.4 × 10-3 ± 0.4 vs HCV 2.1 × 10-3 ± 0.5; p = 0.1680). The proportion of synonymous substitutions to potential synonymous sites was similar (3.667 ± 0.6667 and 2.183 ± 0.9048, respectively; p = 0.2573), and Shannon's entropy values did not differ between HIV-1 and HCV (0.84 ± 0.02 and 0.83 ± 0.12, respectively; p = 0.9408). Of note, 65% (HIV-1) and 67% (HCV) of the analyzed enzymes displayed detectable protease activity, suggesting that both proteases have a similar mutational robustness. In both viruses, there was a rugged protease enzymatic activity landscape characterized by a sharp peak, representing the master sequence, surrounded by a collection of diverse variants present at lower frequencies. These results indicate that nucleotide quasispecies diversification during chronic infection may not be responsible for the higher worldwide genetic diversity observed in HCV.


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Miguel Angel Martinez, Maria Nevot, Ana Jordan-Paiz and Sandra Franco.


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Grups d’IrsiCaixa vinculats: Variabilitat genètica i fenotípica del VIH i del VHC