Abstract
A major challenge in the development of a cure for human immunodeficiency virus (HIV) has been the incomplete understanding of the basic mechanisms underlying HIV persistence during antiretroviral therapy. It is now realized that the establishment of a latently infected reservoir refractory to immune system recognition has thus far hindered eradication efforts. Recent investigation into the innate immune response has shed light on signaling pathways downstream of the immunological synapse critical for T-cell activation and establishment of T-cell memory. This has led to the understanding that the cell-to-cell contacts observed in an immunological synapse that involve the CD4+ T cell and antigen-presenting cell or T-cell–T-cell interactions enhance efficient viral spread and facilitate the induction and maintenance of latency in HIV-infected memory T cells. This review focuses on recent work characterizing the immunological synapse and the signaling pathways involved in T-cell activation and gene regulation in the context of HIV persistence.
Highlights
Lymph nodes (LNs) were identified as major sites of viral replication in human immunodeficiency virus (HIV)-infected subjects [1, 2]
Interruption of antiretroviral therapy (ART) almost invariably leads to the reemergence of detectable viral replication even after years of continuous optimal suppressive therapy, thereby demonstrating the presence of a long-lived viral reservoir constituted of a pool of cells capable of producing replication-competent HIV [15]
One mechanism of HIV persistence during prolonged ART is the long-term survival of latently infected quiescent memory CD4+ T cells, which may serve as a reservoir that contributes to viral load rebound after cessation of ART
Summary
Lymph nodes (LNs) were identified as major sites of viral replication in HIV-infected subjects [1, 2]. A large number of studies in humans and non-human primates have reported higher frequencies of HIV/SIV-infected cells as well as higher copy numbers of viral transcripts in CD4+ T cells isolated from lymphoid tissues (GALT, LN) when compared with the peripheral blood [1, 5,6,7,8]. This enrichment in HIV-infected cells can be attributed to several important characteristics of lymphoid tissues.
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