Identification of a CCR5-Expressing T Cell Subset That Is Resistant to R5-Tropic HIV Infection
Open Access
- 27 April 2007
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLoS Pathogens
- Vol. 3 (4) , e58
- https://doi.org/10.1371/journal.ppat.0030058
Abstract
Infection with HIV-1 perturbs homeostasis of human T cell subsets, leading to accelerated immunologic deterioration. While studying changes in CD4+ memory and naïve T cells during HIV-1 infection, we found that a subset of CD4+ effector memory T cells that are CCR7−CD45RO−CD45RA+ (referred to as TEMRA cells), was significantly increased in some HIV-infected individuals. This T cell subset displayed a differentiated phenotype and skewed Th1-type cytokine production. Despite expressing high levels of CCR5, TEMRA cells were strikingly resistant to infection with CCR5 (R5)–tropic HIV-1, but remained highly susceptible to CXCR4 (X4)–tropic HIV-1. The resistance of TEMRA cells to R5-tropic viruses was determined to be post-entry of the virus and prior to early viral reverse transcription, suggesting a block at the uncoating stage. Remarkably, in a subset of the HIV-infected individuals, the relatively high proportion of TEMRA cells within effector T cells strongly correlated with higher CD4+ T cell numbers. These data provide compelling evidence for selection of an HIV-1–resistant CD4+ T cell population during the course of HIV-1 infection. Determining the host factors within TEMRA cells that restrict R5-tropic viruses and endow HIV-1–specific CD4+ T cells with this ability may result in novel therapeutic strategies against HIV-1 infection. HIV-1 infection profoundly perturbs the immune system and is characterized by depletion of CD4+ T cells and chronic immune activation, which lead to AIDS. Although HIV-1 targets CD4+ T cells, it also requires a second receptor in order to infect the target cells. The majority of HIV-1 strains that are transmitted use a cell surface molecule called CCR5, which is expressed on a portion of T cells. In this manuscript we identify a subset of human CD4+ T cells, which we termed TEMRA cells, that express CCR5 but still remain resistant to infection. We show that HIV-1 infection is blocked in TEMRA cells after entry of the virus, but before it has a chance to integrate into the cellular genome. TEMRA cells are present at low frequency in HIV-1 uninfected individuals but greatly increase in some HIV-infected individuals, which correlates with higher CD4+ T cell numbers. These findings provide the basis for future studies to understand the role of TEMRA cells during HIV-1 infection and identify the host factors that could restrict the virus. This knowledge may be used to endow susceptible T cells with the ability to resist infection and result in novel vaccine or therapeutic strategies against HIV-1 infection.Keywords
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