The HIV-1 Envelope Transmembrane Domain Binds TLR2 through a Distinct Dimerization Motif and Inhibits TLR2-Mediated Responses

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To understand viral pathology and the tools needed to eliminate infection, it is important to understand how viral immune evasion occurs. One such mode of inhibition is the decreased responsiveness of Toll-Like Receptors (TLRs). To date, the exact mechanism inducing this inhibition is not clear. In this study, we utilized a multidisciplinary approach and report on direct modulation of TLR2 activity by the envelope trans-membrane protein of HIV-1 through trans-membrane domain interactions. This interaction resulted in a decreased response in vitro of TLR2 to its natural ligand LTA. Through mutagenesis analysis we show that the GxxxG motif is the driving force of this interaction. Interestingly, the inhibitory effect was also highly effective in protecting mice from lethal effects in a sepsis-like model. Our findings implicate that ENV participates in innate immune impairment, which may occur during viral entry and at latent stages. Furthermore, due to the high functional homology between viral ENV proteins, this function may exhibit a general character of viral-induced immune modulation.

Vyšlo v časopise: The HIV-1 Envelope Transmembrane Domain Binds TLR2 through a Distinct Dimerization Motif and Inhibits TLR2-Mediated Responses. PLoS Pathog 10(8): e32767. doi:10.1371/journal.ppat.1004248
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004248

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