HIV-1 Pathogenesis: The Virus

Swanstrom, Ronald; Coffin, John M.

doi:10.1101/cshperspect.a007443

Cited by 115 publications

(107 citation statements)

References 142 publications

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“…It has been suggested that the replication ability of primate lentiviruses in unusual hosts is more severely affected, via an interferon-induced antiviral state mediated by unidentified species-specific factors, than that in natural hosts (23). Moreover, there are the other significant issues to be considered, such as viral coreceptor tropism (CXCR4 versus CCR5), the diversity in viral growth properties (HIV-1 versus SIVmac), and the difference in host immune responses (human versus RhM) (9,(65)(66)(67). Most importantly, CCR5-tropic but not CXCR4-tropic clones have been found to be appropriate as input viruses to experimentally infect RhMs for various HIV-1 model studies in vivo (65)(66)(67).…”

Section: Discussionmentioning

confidence: 99%

Generation of Rhesus Macaque-Tropic HIV-1 Clones That Are Resistant to Major Anti-HIV-1 Restriction Factors

Nomaguchi

Yokoyama

Kono

et al. 2013

J Virol

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h Human immunodeficiency virus type 1 (HIV-1) replication in macaque cells is restricted mainly by antiviral cellular APOBEC3, TRIM5␣/TRIM5CypA, and tetherin proteins. For basic and clinical HIV-1/AIDS studies, efforts to construct macaque-tropic HIV-1 (HIV-1mt) have been made by us and others. Although rhesus macaques are commonly and successfully used as infection models, no HIV-1 derivatives suitable for in vivo rhesus research are available to date. In this study, to obtain novel HIV-1mt clones that are resistant to major restriction factors, we altered Gag and Vpu of our best HIV-1mt clone described previously. First, by sequence-and structure-guided mutagenesis, three amino acid residues in Gag-capsid (CA) (M94L/R98S/G114Q) were found to be responsible for viral growth enhancement in a macaque cell line. Results of in vitro TRIM5␣ susceptibility testing of HIV-1mt carrying these substitutions correlated well with the increased viral replication potential in macaque peripheral blood mononuclear cells (PBMCs) with different TRIM5 alleles, suggesting that the three amino acids in HIV-1mt CA are involved in the interaction with TRIM5␣. Second, we replaced the transmembrane domain of Vpu of this clone with the corresponding region of simian immunodeficiency virus SIVgsn166 Vpu. The resultant clone, MN4/LSDQgtu, was able to antagonize macaque but not human tetherin, and its Vpu effectively functioned during viral replication in a macaque cell line. Notably, MN4/ LSDQgtu grew comparably to SIVmac239 and much better than any of our other HIV-1mt clones in rhesus macaque PBMCs. In sum, MN4/LSDQgtu is the first HIV-1 derivative that exhibits resistance to the major restriction factors in rhesus macaque cells.

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Section: Discussionmentioning

confidence: 99%

Generation of Rhesus Macaque-Tropic HIV-1 Clones That Are Resistant to Major Anti-HIV-1 Restriction Factors

Nomaguchi

Yokoyama

Kono

et al. 2013

J Virol

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“…As discussed by Swanstrom and Coffin (2011), HIV can be found in a large number of organs and tissues. In some sites, such as the central nervous system (CNS), there is a clear genetic separation of independently evolving populations, often leading to macrophage-tropic viruses that likely replicate in either macrophages or microglial cells in the brain.…”

Section: Course Of Evolution Following Infectionmentioning

confidence: 99%

HIV Pathogenesis: Dynamics and Genetics of Viral Populations and Infected Cells

Coffin

Swanstrom

2013

Cold Spring Harbor Perspectives in Medicine

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120

121

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“…At this point, the cells are significantly more prone to infection with HIV-1. Indeed, resting monocytes are very difficult to infect in vitro (70). That HIV-1 can very clearly infect MDM in vitro suggests that macrophages could support viral replication in vivo.…”

Section: Evidence That Macrophages Support Viral Replicationmentioning

confidence: 99%

“…A new viral nomenclature then emerged in which M-tropic viruses are R5 tropic and T-tropic viruses are X4 tropic (68). Though only a minority of CD4 T cells in the peripheral blood express CCR5, the majority of CD4 T cells within the GI tract express CCR5, and the vast majority of transmitted viruses are R5 tropic, with X4-tropic viruses generally emerging very late in infection (69)(70)(71).…”

Section: Evidence That Macrophages Support Viral Replicationmentioning

confidence: 99%

“…The vast majority of CCR5-tropic HIV strains do not infect myeloid cells in vitro and might, instead, be classified as "R5 T cell tropic" (46,48,70,74). Thus, a new nomenclature system has been suggested: R5 T cell tropic (the vast majority of viruses isolated from patients), R5 macrophage tropic (that evolve late in untreated infection to have a relatively higher affinity for CD4), and X4 T cell tropic (that evolve only late in infection) (70).…”

Section: Evidence That Macrophages Support Viral Replicationmentioning

confidence: 99%

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Macrophages in Progressive Human Immunodeficiency Virus/Simian Immunodeficiency Virus Infections

DiNapoli

Hirsch

Brenchley

2016

J Virol

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The cells that are targeted by primate lentiviruses (HIV and simian immunodeficiency virus [SIV]) are of intense interest given the renewed effort to identify potential cures for HIV. These viruses have been reported to infect multiple cell lineages of hematopoietic origin, including all phenotypic and functional CD4 T cell subsets. The two most commonly reported cell types that become infected in vivo are memory CD4 T cells and tissue-resident macrophages. Though viral infection of CD4 T cells is routinely detected in both HIV-infected humans and SIV-infected Asian macaques, significant viral infection of macrophages is only routinely observed in animal models wherein CD4 T cells are almost entirely depleted. Here we review the roles of macrophages in lentiviral disease progression, the evidence that macrophages support viral replication in vivo, the animal models where macrophage-mediated replication of SIV is thought to occur, how the virus can interact with macrophages in vivo, pathologies thought to be attributed to viral replication within macrophages, how viral replication in macrophages might contribute to the asymptomatic phase of HIV/SIV infection, and whether macrophages represent a long-lived reservoir for the virus. Macrophages are a diverse and functionally important component of the immune system. Evolutionarily conserved in almost all species of the phylum Chordata, macrophages are one of the "oldest" leukocyte lineages and have the highest degree of plasticity across leukocyte subsets (1). Macrophages differentiate from the yolk sac, fetal liver, and peripheral blood monocytes that developed from bone marrow-derived hematopoietic stem cells. With their phenotypic and functional plasticity and presence in disparate tissues, macrophages play supportive roles in multiple aspects of physiology. Their function often depends upon their anatomical location, their individual ontogeny, and extracellular cues. For example, macrophages derived from the yolk sac or fetal liver reside in organs such as the brain (as microglia cells), pancreas, spleen, liver (as Kuppfer cells), and kidney. For many years, yolk sac-and fetal liver-derived macrophages were thought to be very long-lived, perhaps for the life span of the host. Indeed, after differentiating during fetal development, these macrophages can populate tissues for the duration of the host's life. However, recent data suggest that these cells can also divide in vivo to maintain homeostasis (1-3) and are able to rapidly repopulate after chemotherapeutic depletion (in the case of brain-resident microglia cells [4]). Our understanding of macrophage longevity and factors important for their homeostatic proliferation in vivo is incomplete and more data are required. FUNCTIONS OF MACROPHAGES IN HEALTHThough macrophage longevity is not fully understood, many studies have demonstrated that tissue-resident macrophages have critically important functions in tissue immunity and repair, antigen presentation, and tissue homeostasis. Indeed, the importance of their fu...

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HIV-1 Pathogenesis: The Virus

Cited by 115 publications

References 142 publications

Generation of Rhesus Macaque-Tropic HIV-1 Clones That Are Resistant to Major Anti-HIV-1 Restriction Factors

Generation of Rhesus Macaque-Tropic HIV-1 Clones That Are Resistant to Major Anti-HIV-1 Restriction Factors

HIV Pathogenesis: Dynamics and Genetics of Viral Populations and Infected Cells

Macrophages in Progressive Human Immunodeficiency Virus/Simian Immunodeficiency Virus Infections

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