Circulating Monocytes Are Not a Major Reservoir of HIV-1 in Elite Suppressors

Spivak, Adam M.; Salgado, María; Rabi, S. Alireza; O’Connell, Karen A.; Blankson, Joel N.

doi:10.1128/jvi.05409-11

Cited by 21 publications

(23 citation statements)

References 61 publications

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“…Studies have shown that ES CD4 + T cells have lower levels of total [5,48] and integrated [28] HIV DNA, and replication-competent HIV-1 [29] compared to patients on suppressive HAART regimens. It is possible that precursors of latently infected cells are cells that were infected as they were transitioning from activated to a resting state, resulting in a non-productively infected cell.…”

Section: Resultsmentioning

confidence: 99%

Primary CD8+ T cells from elite suppressors effectively eliminate non-productively HIV-1 infected resting and activated CD4+T cells

2013

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BackgroundElite controllers or suppressors have the remarkable capacity to maintain HIV-1 plasma RNA levels below the limit of detection of clinical assays (<50 copies/mL) without therapy and have a lower frequency of latently infected cells compared to chronic progressors. While it is unclear how this reduced seeding of the reservoir is achieved, it is possible that effective CTL responses play an in important role in limiting the size of the latent reservoir.ResultsHerein, we demonstrate that primary CD8+ T cells from HLA-B*57/5801 elite suppressors were able to efficiently eliminate resting and activated primary CD4+ T cells shortly after viral entry and prior to productive infection. CD8+ T cells from elite suppressors were significantly more effective at eliminating these cells than CD8+ T cells from chronic progressors.ConclusionsNonproductively infected CD4+ T cells may represent a subpopulation of cells that are precursors to latently infected cells; therefore, the effective elimination of these cells may partially explain why elite suppressors have a much lower frequency of latently infected cells compared to chronic progressors. Thus, a vaccine strategy that elicits early and potent CD8+ T cell responses may have the capacity to limit the seeding of the latent reservoir in HIV-1 infection.

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Section: Resultsmentioning

confidence: 99%

Primary CD8+ T cells from elite suppressors effectively eliminate non-productively HIV-1 infected resting and activated CD4+T cells

2013

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“…Total proviral DNA in resting CD4 + T cells was quantified using a real-time PCR assay (Durand et al, 2012). Copy numbers of the human RNaseP gene copies were measured in separate reactions to quantify cell number (TaqMan Copy Number Reference Assay, RNaseP, Invitrogen)(Spivak et al, 2011). …”

Section: Methodsmentioning

confidence: 99%

Replication-Competent Noninduced Proviruses in the Latent Reservoir Increase Barrier to HIV-1 Cure

Shan

Hosmane

et al. 2013

Cell

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“…The only other cell type in the blood reported to be infected is monocytes. A number of studies report the detection of HIV-1 DNA in monocytes (Wang et al 2013; Xu et al 2008; Zhu et al 2002) and the isolation of replication competent virus (Lambotte et al 2000; Sonza et al 2001; Wang et al 2013) from monocytes, but T cells are clearly infected with much greater frequency than monocytes (Fulcher et al 2004; Lambotte et al 2000; Spivak et al 2011) and some investigators have failed to find viral DNA in monocytes above levels that could be accounted for by T-cell contamination (Spivak et al 2011). …”

Section: Hiv-1 In the Blood Is R5 T Cell-tropicmentioning

confidence: 99%

HIV-1 target cells in the CNS

et al. 2014

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HIV-1 replication in the central nervous system (CNS) is typically limited by the availability of target cells. HIV-1 variants that are transmitted and dominate the early stages of infection almost exclusively use the CCR5 coreceptor and are well adapted to entering, and thus infecting, cells expressing high CD4 densities similar to those found on CD4+ T cells. While the “immune privileged” CNS is largely devoid of CD4+ T cells, macrophage and microglia are abundant throughout the CNS. These cells likely express CD4 densities that are too low to facilitate efficient entry or allow sustained replication by most HIV-1 isolates. Examination of CNS viral populations reveals that late in disease the CNS of some individuals contains HIV-1 lineages that have evolved the ability to enter cells expressing low levels of CD4 and are well-adapted to entering macrophages. These macrophage-tropic (M-tropic) viruses are able to maintain sustained replication in the CNS for many generations, and their presence is associated with severe neurocognitive impairment. Whether conditions such as pleocytosis are necessary for macrophage-tropic viruses to emerge in the CNS is unknown, and extensive examinations of macrophage-tropic variants have not revealed a genetic signature of this phenotype. It is clear, however, that macrophage tropism is rare among HIV-1 isolates and is not transmitted, but is important due to its pathogenic effects on hosts. Prior to the evolution of macrophage-tropic variants, the viruses that are predominately infecting T cells (R5 T cell-tropic) may infect macrophages at a low level and inefficiently, but this could contribute to the reservoir.

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Circulating Monocytes Are Not a Major Reservoir of HIV-1 in Elite Suppressors

Cited by 21 publications

References 61 publications

Primary CD8+ T cells from elite suppressors effectively eliminate non-productively HIV-1 infected resting and activated CD4+T cells

Primary CD8+ T cells from elite suppressors effectively eliminate non-productively HIV-1 infected resting and activated CD4+T cells

Replication-Competent Noninduced Proviruses in the Latent Reservoir Increase Barrier to HIV-1 Cure

HIV-1 target cells in the CNS

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