HIV-2/SIV Vpx Protein Interacts with Human Nup153 and Regulates Viral Pathogenesis

Abstract

Methods:We initially determined whether pseudovirus-Envs from transmitted founders (TF) had enhanced DC-SIGN binding, trans-infection and increased IL-10 secretion over matched chronic Envs. As DC-SIGN interactions with Env favors high mannose N-glycans, we also deleted gp120 PNGs bearing high mannose glycans either singly, or in combination, in matched CAP239 Env T/F and chronic clones. Results: T/F Envs induced more IL-10 secretion than chronic controls. When PNGs were deleted from the CAP239 envs, the effect on pseudovirion entry, DC-SIGN binding and transinfection was clone specific, suggesting that specific N-glycans affect Env function differently in different clones. For example deletion of PNG 448 reduced entry efficiency, DC-SIGN binding and trans-infection of TF by *50% when compared to wild type, while either enhancing or maintaining these phenotypes in the chronic infection clone. Only deletion of the PNG 241 reduced IL-10 induction for T/F clones. Conclusions: As pseudovirion entry efficiencies of most PNG mutants were reduced for both CAP239 Env clones, it is difficult to determine the role that each might play in DC-SIGN interactions. However, the TF Envs induced MDDCs to secrete higher levels of IL-10 compared to matched chronic infection controls, suggesting that localized anti-inflammatory responses in the genital epithelium might play a role in HIV transmission.