Different Infectivity of HIV-1 Strains Is Linked to Number of Envelope Trimers Required for Entry

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Our estimates of the HIV-1 entry stoichiometry, that is the number of envelope glycoprotein trimers needed to mediate fusion of viral and target cell membrane, close an important gap in our understanding of the HIV entry process. As we show, stoichiometric requirements for envelope trimers differ between HIV strains and steer virus entry efficacy and virus entry kinetics. Thus, the entry stoichiometry has important implications for HIV transmission, as demands on trimer numbers will dictate the infectivity of virus populations, target cell preferences and virus inactivation by trimer-targeting inhibitors and neutralizing antibodies. Beyond this, our data contribute to the general understanding of mechanisms and energetic requirements of protein-mediated membrane fusion, as HIV entry proved to follow similar stoichiometries as described for Influenza virus HA and SNARE protein mediated membrane fusion. In summary, our findings provide a relevant contribution towards a refined understanding of HIV-1 entry and pathogenesis with particular importance for ongoing efforts to generate neutralizing antibody based therapeutics and vaccines targeting the HIV-1 envelope trimer.

Vyšlo v časopise: Different Infectivity of HIV-1 Strains Is Linked to Number of Envelope Trimers Required for Entry. PLoS Pathog 11(1): e32767. doi:10.1371/journal.ppat.1004595
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004595

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