Huntingtin-interacting Protein 1 Promotes Vpr-induced G2 Arrest and HIV-1 Infection in Macrophages

Abstract Background: Human immunodeficiency virus type 1 (HIV-1) modulates the host cell cycle. The HIV-1 accessory protein Vpr arrests the cell cycle at G2 phase, which is important for efficient viral replication in dividing CD4+ T cells, because the transcriptional activity of the HIV-1 long terminal repeat is most active in G2 phase. Additionally, Vpr-mediated G2 arrest likely correlates with enhanced HIV-1 infection in monocyte-derived macrophages.Results: Here, we screened small-interfering RNA to reveal candidates that suppress Vpr-induced G2 arrest and identified Huntingtin-interacting protein 1 (HIP1) as both directly interacting with Vpr and required for efficient G2 arrest. Interestingly, HIP1 was not essential for Vpr-induced DNA double-strand breaks, which are required for activation of the DNA-damage checkpoint and G2 arrest. Furthermore, HIP1 knockdown suppressed HIV-1 infection in monocyte-derived macrophages.Conclusions: These results suggest that HIP1 operates in the downstream step(s) of DNA-damage induction to promote Vpr-induced G2 arrest and enhances HIV-1 infection in macrophages.