Distinct memory CD4⁺ T cell subset tropism of two CCR5-tropic HIV-1 in a rapid progressor

Low HIV-1 infection level in the central memory CD4⁺ T cell subset is a hallmark of both non-progressive HIV infection and non-pathogenetic SIV infection in the natural hosts. However, an important gap in knowledge is whether CCR5-tropic HIV-1 variants have different memory CD4⁺ T cell subset preferences.

Here, we identified clear compartmentalization of two CCR5-tropic HIV-1 in different memory CD4⁺ T cell subsets in a rapid progressor. Participant 40512 was identified in the RV217 cohort. While the transmitted/founder (T/F) virus in 40512 was compartmentalized in the central memory CD4⁺ T cells, the superinfecting virus was compartmentalized in the effector memory CD4⁺ T cells. Both viruses rely on CCR5 to infect primary CD4⁺ T cells. The T/F virus is more than 100-fold more resistant to the CCR5 inhibitor Maraviroc than the superinfecting virus.

This case report demonstrates that CCR5 HIV-1 variants have distinct memory CD4⁺ T cell subset preferences in vivo. Because CD4⁺ T cell subset targeting is highly relevant for HIV-1 pathogenesis, understanding the underlying molecular mechanisms may provide deeper insights into HIV-1 therapeutics and functional cure.