The Quest for Cellular Markers of HIV Reservoirs: Any Color You Like

Abstract

Combination antiretroviral therapy (ART) suppresses human immunodeficiency virus (HIV) replication and improves immune function, but is unable to eradicate the virus. Therefore, development of an HIV cure has become one of the main priorities of the HIV research field. The main obstacle for an HIV cure is the formation of latent viral reservoirs, where the virus is able to “hide” despite decades of therapy, just to reignite active replication once therapy is stopped. Revealing HIV hiding places is thus central to HIV cure research, but the absence of markers of these reservoir cells greatly complicates the search for a cure. Identification of one or several marker(s) of latently infected cells would represent a significant step forward toward a better description of the cell types involved and improved understanding of HIV latency. Moreover, it could provide a “handle” for selective therapeutic targeting of the reservoirs. A number of cellular markers of HIV reservoir have recently been proposed, including immune checkpoint molecules, CD2, and CD30. CD32a is perhaps the most promising of HIV reservoir markers as it is reported to be associated with a very prominent enrichment in HIV DNA, although this finding has been challenged. In this review, we provide an update on the current knowledge about HIV reservoir markers. We specifically highlight studies that characterized markers of persistently infected cells in the lymphoid tissues.

Current Status of Latency Reversing Agents Facing the Heterogeneity of HIV-1 Cellular and Tissue Reservoirs

“…Recently, the expression of CD32a has been reported as a potential marker of memory CD4 + T cells harboring a replication-competent latent virus in aviremic patients under ART (Descours et al, 2017;Darcis et al, 2019). The role of CD32a as a cellular marker of HIV-1 reservoirs has been the subject of several works Martin et al, 2018;Osuna et al, 2018;Thornhill et al, 2019).…”

Key Players in HIV-1 Transcriptional Regulation: Targets for a Functional Cure

“…This is a very tall order, given that we have no specific marker to distinguish the infected from the uninfected cells. Even if some have been proposed, their identification remains very difficult [204][205][206][207][208][209]. An obstacle in assessing the efficacy of cure strategies is the accurate determination of the reservoir size.…”

Differences in HIV Markers between Infected Individuals Treated with Different ART Regimens: Implications for the Persistence of Viral Reservoirs

“…Most of the HIV latent reservoirs reside in various tissues, such as the lymph nodes, the central nervous system, the gut-associated lymphoid tissue, the testes, and the urethra [41][42][43][44][45]. A better understanding of these heterogeneous reservoirs and their evolution during long-term ART is an indispensable prerequisite to the design of strategies aimed at eradicating HIV, and more precise identification of the latently infected cells would facilitate studies of the HIV reservoirs [46].…”