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

## TL;DR

This study shows that two CCR5-tropic HIV-1 viruses prefer different memory CD4+ T cell subsets in a rapid progressor, which could impact HIV treatment and cure strategies.

## Contribution

The study reveals distinct memory CD4+ T cell subset tropism of two CCR5-tropic HIV-1 viruses in a single patient.

## Key findings

- The transmitted/founder virus was compartmentalized in central memory CD4+ T cells.
- The superinfecting virus was compartmentalized in effector memory CD4+ T cells.
- The transmitted/founder virus showed over 100-fold higher resistance to Maraviroc than the superinfecting virus.

## Abstract

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.