HIV-1 infectivity of cells is enhanced at mitosis: a role for Vpr?

Abstract

Restriction factors are present in all cells including non-immune cells and protect them from invading viruses. RNA-associated Early-stage Antiviral Factor (REAF) was identified from a whole genome siRNA screen for restriction factors to HIV-1(1). siRNA induced knockdown of REAF increases viral infectivity, while over-expression of the protein limits infection(2). Here we show that during mitosis, REAF is specifically excluded from the chromatin region and that mitotic cells have an increased susceptibility to HIV-1. We also demonstrate that in HIV-1 infection of monocyte-derived macrophages, Vpr is responsible for the degradation of nuclear REAF. Furthermore, silencing REAF expression in cycling cells by RNAi causes cells to accumulate in the G2/M phase. This result is consistent with previous observations that Vpr induces cell cycle arrest after infection (3). 1. L. Liu et al., A whole genome screen for HIV restriction factors. Retrovirology 8, 94 (2011). 2. K. M. Marno et al., Novel restriction factor RNA-associated early-stage anti-viral factor (REAF) inhibits human and simian immunodeficiency viruses. Retrovirology 11, 3 (2014). 3. J. B. Jowett et al., The human immunodeficiency virus type 1 vpr gene arrests infected T cells in the G2+M phase of the cell cycle. J Virol 69, 6304–6313 (1995).