KLF2 expression modulates susceptibility to HIV-1 infection (154.25)

Abstract

Abstract Here, we show that the transcription factor KLF2 is a host factor with a role in modulating susceptibility to HIV-1 infection. We observed a strong correlation between expression of KFL2 and CCR5. Transformed CD4 T cell lines lack CCR5 as well as KLF2 expression. Forced expression of KFL2 in transformed cell lines induced CCR5 expression and rendered them susceptible to R5 HIV-1 infection, providing insight into why most transformed lines fail to support CCR5 dependent HIV-1 replication. In primary human CD4 T cells, KFL2 expression is rapidly downregulated after T cell activation and is undetectable after anti-CD3/28 costimulation, whereas trace amounts remain after PHA + IL-2 stimulation. This residual amount of KLF2 present after T cell activation correlates well with CCR5 expression and susceptibility to R5 infection. Primary human CD4 T engineered to constitutively express KLF2 retained CCR5 expression and susceptibility to R5 infection after CD3/28 costimulation. These studies implicate KLF2 expression levels present after T cell activation as the determinant of whether a T cell is susceptible to R5 HIV-1 infection. Thus, KLF2 is a host factor that could affect an individual’s susceptibility to HIV-1 infection and the rate by which one progresses to AIDS.