In vivo role for Vpr

Of the four accessory proteins expressed by human immunodeficiency virus type 1 (HIV-1), Vpr is the least well understood. In PLoS Pathogens, Koyanagi and colleagues use a humanized mouse model to demonstrate the important role of Vpr in accelerating HIV-1 replication. Regulatory T cells (T_reg cells) show 'preferential' infection with CCR5-tropic HIV-1, but not with CXCR4-tropic HIV-1, by virtue of their inherently high turnover rate and high expression of the entry coreceptor CCR5. Infection of T_reg cells by HIV-1 results in their apoptosis and concomitant generalized activation of the immune system. Similarly, pharmacological depletion of T_reg cells leads to the activation and proliferation of conventional T cells and a higher viral burden. Mutants with defective Vpr, however, show less infection and loss of T_reg cells as well as a lower viral burden. The decrease in T_reg cell numbers through the action of Vpr thus leads to impaired homeostatic regulation of conventional T cells and thereby increases the pool of activated cell targets and optimal HIV-1 replication.

PLoS Pathog. (5 December 2013) doi:10.1371/journal.ppat.1003812