AI Article Synopsis
- The HIV-1 accessory protein Vpu is crucial for the virus's ability to evade the innate immune system by down-regulating the CD1d molecule on infected dendritic cells.
- Research indicates that this down-regulation function of Vpu is conserved across various HIV-1 groups and related primate viruses, although subtype C Vpu proteins are less effective than subtype B.
- Key discoveries highlight specific residues in the cytoplasmic domain of Vpu, particularly a C-terminal APW motif in subtype B, that are essential for reducing CD1d surface expression and contribute to the virus's immune evasion strategies.
Article Abstract
The HIV-1 accessory protein Vpu is emerging as a critical factor for viral evasion from innate immunity. We have previously shown that the Vpu proteins of two HIV-1 group M subtype B strains (NL4-3 and BaL) down-regulate CD1d from the surface of infected dendritic cells (DCs) and inhibit their crosstalk with the innate invariant natural killer T (iNKT) cells. In the present study, we have investigated the ability of a comprehensive set of primate lentiviral Vpu proteins to interfere with CD1d-mediated immunity. We found that CD1d down-regulation is a conserved function of Vpu proteins from HIV-1 groups M, O and P as well as their direct precursors SIVcpzPtt and SIVgor. At the group M subtype level, subtype C Vpu proteins were significantly weaker CD1d antagonists than subtype B Vpu proteins. Functional characterization of different mutants and chimeras derived from active subtype B and inactive subtype C Vpu proteins revealed that residues in the cytoplasmic domain are important for CD1d down-regulation. Specifically, we identified a C-terminal APW motif characteristic for group M subtype B Vpu proteins necessary for interference with CD1d surface expression. These findings support the notion that Vpu plays an important role in lentiviral evasion from innate immunity.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4397644 | PMC |
| http://dx.doi.org/10.1038/srep09675 | DOI Listing |
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