HIV-2 Vpx Interacts with IRF5 and Inhibits its Function [Molecular Bases of Disease]

February 14th, 2014 by Cheng, X., Ratner, L.

Interferon regulatory factor (IRF) family members have been implicated as critical transcription factors that function in immune responses, hematopoietic differentiation, and cell growth regulation. Activation of IRF5 results in the production of pro-inflammatory cytokines such as TNFα, IL6 and IL12, as well as type I interferons. In this study we demonstrate that HIV-2 Vpx interacts with IRF5, and Vpx inhibits IRF5-mediated transactivation. Expression of Vpx in THP-1 cells reduced mRNA levels and protein production of Toll-like receptor (TLR) dependent IL6, IL12p40 and TNFα induced by lipopolysaccharide (LPS), R848 and ODN2216. Chromatin immunoprecipitation assays show that Vpx expression results in decreased promoter binding activity of IRF5. This study provides new insights into mechanisms employed by HIV-2 to counteract innate immune defenses against viral infection.