Abstract
As we learn more about the HIV latent reservoir, we continue to discover that the viral reservoir is more complicated than just a pool of infected resting memory CD4+ T cells in peripheral blood. Evidence increasingly points to both certain tissues and certain types of cells as potential viral reservoirs. T follicular helper cells (TFH) are prime targets of HIV infection—this creates a sanctuary for infected cells because CD8+ T cells generally do not enter lymph node follicles unless they express CXCR5, and are not as effective at killing infected CD4+ T cells as peripheral CD8+ T cells. In this review, we summarize the current state of research on TFH cell infection in peripheral lymphoid tissues and focus on the question of whether CD8+ T cell exclusion from B cell follicles is responsible, at least in part, for establishing secondary lymphoid tissue B cell follicles as an anatomic site of HIV transcription and replication.
Highlights
As we approach the 5th decade of the HIV pandemic and after years of intensive cure study, we continue to find a cure for HIV outside the reach of natural immunity due to the persistence of the latent reservoir found in resting memory CD4+ T cells
Years of HIV and Simian immunodeficiency virus (SIV) latency research has revealed several important conclusions, first that lymphoid tissues represent a major site for HIV replication in viremic individuals and a significant reservoir of inducible virus in patients on antiretroviral therapy (ART)
CD4+ helper T cells are more likely to be productively infected within lymphoid follicles compared to extrafollicular sites
Summary
As we approach the 5th decade of the HIV pandemic and after years of intensive cure study, we continue to find a cure for HIV outside the reach of natural immunity due to the persistence of the latent reservoir found in resting memory CD4+ T cells. Because of a lack of ongoing viral replication, suppressive antiretroviral therapy (ART) does not effectively target latently infected CD4+ T cells and a study by Siliciano et al estimated that it will take more than 73 years for an HIV-infected individual to clear the latent reservoir with ART alone [6]. Most studies of the latent reservoir have been done exclusively using peripheral blood mononuclear cells (PBMCs). This presents a problem for accurate estimation of the size of the reservoir as many lymphocytes in the body reside in the lymphatic system and tissues. Throughout the body there are likely other reservoirs and sanctuaries for HIV which may have different characteristics from the peripheral blood reservoir [7]
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