Blog
About

  • Record: found
  • Abstract: found
  • Article: not found

Cytomegalovirus and HIV Persistence: Pouring Gas on the Fire.

AIDS Research and Human Retroviruses

Mary Ann Liebert, Inc.

HIV, CMV, reservoir, persistence, inflammation

Read this article at

ScienceOpenPublisherPMC
Bookmark
      There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

      Abstract

      The inherent stability of a small population of T cells that are latently infected with HIV despite antiretroviral therapy (ART) remains a stubborn obstacle to an HIV cure. By exploiting the memory compartment of our immune system, HIV maintains persistence in a small subset of quiescent cells with varying phenotypes, thus evading immune surveillance and clinical detection. Understanding the molecular and immunological mechanisms that maintain the latent reservoir will be critical to the success of HIV eradication strategies. Human cytomegalovirus (CMV), another chronic viral infection, frequently co-occurs with HIV and occupies an oversized proportion of memory T cell responses. CMV and HIV have both evolved complex strategies to manipulate our immune system for their own advantage. Given the increasingly clear links between CMV replication, chronic immune activation, and increased HIV reservoirs, we present a closer examination of the interplay between these two chronic coinfections. Here we review the effects of CMV on the immune system and show how they may affect persistence of the latent HIV reservoir during ART. The studies described herein suggest that hijacking of cytokine and chemokine signaling, manipulation of cell development pathways, and transactivation of HIV expression by CMV might be pouring gas on the fire of HIV persistence. Future interventional studies are required to formally determine the extent to which CMV is causally associated with inflammation and HIV reservoir expansion.

      Related collections

      Most cited references 78

      • Record: found
      • Abstract: found
      • Article: not found

      PD-1 and its ligands in tolerance and immunity.

      Programmed death 1 (PD-1) and its ligands, PD-L1 and PD-L2, deliver inhibitory signals that regulate the balance between T cell activation, tolerance, and immunopathology. Immune responses to foreign and self-antigens require specific and balanced responses to clear pathogens and tumors and yet maintain tolerance. Induction and maintenance of T cell tolerance requires PD-1, and its ligand PD-L1 on nonhematopoietic cells can limit effector T cell responses and protect tissues from immune-mediated tissue damage. The PD-1:PD-L pathway also has been usurped by microorganisms and tumors to attenuate antimicrobial or tumor immunity and facilitate chronic infection and tumor survival. The identification of B7-1 as an additional binding partner for PD-L1, together with the discovery of an inhibitory bidirectional interaction between PD-L1 and B7-1, reveals new ways the B7:CD28 family regulates T cell activation and tolerance. In this review, we discuss current understanding of the immunoregulatory functions of PD-1 and its ligands and their therapeutic potential.
        Bookmark
        • Record: found
        • Abstract: found
        • Article: not found

        HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation.

        HIV persists in a reservoir of latently infected CD4(+) T cells in individuals treated with highly active antiretroviral therapy (HAART). Here we identify central memory (T(CM)) and transitional memory (T(TM)) CD4(+) T cells as the major cellular reservoirs for HIV and find that viral persistence is ensured by two different mechanisms. HIV primarily persists in T(CM) cells in subjects showing reconstitution of the CD4(+) compartment upon HAART. This reservoir is maintained through T cell survival and low-level antigen-driven proliferation and is slowly depleted with time. In contrast, proviral DNA is preferentially detected in T(TM) cells from aviremic individuals with low CD4(+) counts and higher amounts of interleukin-7-mediated homeostatic proliferation, a mechanism that ensures the persistence of these cells. Our results suggest that viral eradication might be achieved through the combined use of strategic interventions targeting viral replication and, as in cancer, drugs that interfere with the self renewal and persistence of proliferating memory T cells.
          Bookmark
          • Record: found
          • Abstract: found
          • Article: not found

          CD4+ T Cell Depletion during all Stages of HIV Disease Occurs Predominantly in the Gastrointestinal Tract

          The mechanisms underlying CD4+ T cell depletion in human immunodeficiency virus (HIV) infection are not well understood. Comparative studies of lymphoid tissues, where the vast majority of T cells reside, and peripheral blood can potentially illuminate the pathogenesis of HIV-associated disease. Here, we studied the effect of HIV infection on the activation and depletion of defined subsets of CD4+ and CD8+ T cells in the blood, gastrointestinal (GI) tract, and lymph node (LN). We also measured HIV-specific T cell frequencies in LNs and blood, and LN collagen deposition to define architectural changes associated with chronic inflammation. The major findings to emerge are the following: the GI tract has the most substantial CD4+ T cell depletion at all stages of HIV disease; this depletion occurs preferentially within CCR5+ CD4+ T cells; HIV-associated immune activation results in abnormal accumulation of effector-type T cells within LNs; HIV-specific T cells in LNs do not account for all effector T cells; and T cell activation in LNs is associated with abnormal collagen deposition. Taken together, these findings define the nature and extent of CD4+ T cell depletion in lymphoid tissue and point to mechanisms of profound depletion of specific T cell subsets related to elimination of CCR5+ CD4+ T cell targets and disruption of T cell homeostasis that accompanies chronic immune activation.
            Bookmark

            Author and article information

            Journal
            10.1089/aid.2017.0145
            5684659
            29140108

            HIV, CMV, reservoir, persistence, inflammation

            Comments

            Comment on this article