Th17 cell master transcription factor RORC2 regulates HIV-1 gene expression and viral outgrowth

Abstract

Significance HIV-1 infects CD4 T cells, and, among these, T helper 17 (Th17) cells are known to be particularly permissive for virus replication. The infection of Th17 cells is critical for AIDS pathogenesis and viral persistence. It is, however, not clear why these cells are highly permissive to HIV-1. We found that Th17 cell permissiveness depends on the expression of the hormone receptor RORC2, which is the master transcriptional regulator of Th17 cell differentiation. We identify RORC2 as a cell-specific host-dependency factor that can be targeted by small molecules. Our results suggest that RORC2 may be a cell-specific target to mitigate the loss of Th17 cells as a consequence of their preferential HIV-1 infection.