CD133+ Hematopoietic Progenitor Cells Harbor HIV Genomes in a Subset of Optimally Treated People With Long-Term Viral Suppression

McNamara, Lucy A.; Onafuwa-Nuga, Adewunmi; Sebastian, Nadia T.; Riddell, James; Bixby, Dale; Collins, Kathleen L.

doi:10.1093/infdis/jit118

Cited by 46 publications

(45 citation statements)

References 29 publications

(48 reference statements)

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“…HIV-1 DNA and ACTB DNA were quantified by quantitative PCR (qPCR) using specific primers as described previously (Clouse et al, 1989; McNamara et al, 2013; Norman et al, 2011). Dilutions of ACH-2 DNA (Clouse et al, 1989; Folks et al, 1989) were used to calculate gag copy number and relative DNA input.…”

Section: Experimental Methodsmentioning

confidence: 99%

Vpr Overcomes Macrophage-Specific Restriction of HIV-1 Env Expression and Virion Production

Mashiba

Collins

Terry

et al. 2014

Cell Host & Microbe

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Summary The HIV-1 accessory protein Vpr enhances infection of primary macrophages through unknown mechanisms. Recent studies demonstrated that Vpr interactions with the cellular DCAF1-DDB1-CUL4 E3 ubiquitin ligase complex limit activation of innate immunity and interferon (IFN) induction. We describe a restriction mechanism that targets the HIV-1 envelope protein Env but is overcome by Vpr and its interaction with DCAF1. This restriction is active in the absence of Vpr in HIV-1-infected primary macrophages and macrophage-epithelial cell heterokaryons, but not epithelial cell lines. HIV-1-infected macrophages lacking Vpr express more IFN following infection, target Env for lysosomal degradation and produce fewer Env-containing virions. Conversely, Vpr expression reduces IFN induction, rescues Env expression and enhances virion release. Addition of IFN or silencing DCAF1 reduces the amount of cell-associated Env and virion production in wild-type HIV-1-infected primary macrophages. These findings provide insight into an IFN-stimulated macrophage-specific restriction pathway targeting HIV-1 Env that is counteracted by Vpr.

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Section: Experimental Methodsmentioning

confidence: 99%

Vpr Overcomes Macrophage-Specific Restriction of HIV-1 Env Expression and Virion Production

Mashiba

Collins

Terry

et al. 2014

Cell Host & Microbe

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“…25 A recent study extended these findings to the CD133 ϩ cohort within the BM of patients on cART. 26 Studies evaluating hematopoiesis in patients undergoing HIV treatment also support a direct role for the virus in inducing anemia. In animal studies of HIV infection using glycolipid administration to activate natural killer cells, decreased HIV-1 viral replication was accompanied by restoration of normal hematopoiesis in treated mice.…”

Section: Multifactorial Pathogenesis Of Anemia In Hivmentioning

confidence: 99%

Pathogenesis and clinical implications of HIV-related anemia in 2013

Redig¹,

2013

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Anemia is a common feature of HIV-related disease and has been uniformly demonstrated to be an independent predictor of morbidity and mortality. Although anemia often responds to combination antiretroviral therapy, many patients remain anemic despite therapy and such persistent anemia continues to negatively affect prognosis regardless of drug response. Anemia is also a common feature of normal aging. We postulate that the pathophysiology of anemia in HIV, especially that which persists in the face of combination antiretroviral therapy, is a reflection of underlying proinflammatory pathways that are also thought to contribute to anemia in the elderly, as well as other age-related chronic diseases such as cardiovascular disease and chronic obstructive pulmonary disease. This suggests that HIV induces inflammatory pathways that are associated with a pattern of accelerated aging and that anemia is a biomarker of these processes. A better understanding of the pathophysiology of HIV-related anemia may provide important entry points for improving the chronic manifestations of HIV-related disease.

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“…HIV provirus has been identified within these cells in some donors [8] and the significance of this reservoir is a subject of ongoing research. As HSPCs are even more rare than T SCM , the reservoir is likely to be even smaller.…”

mentioning

confidence: 99%

Long-lived reservoirs of HIV-1

Zaikos

Collins

2014

Trends in Microbiology

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CD133+ Hematopoietic Progenitor Cells Harbor HIV Genomes in a Subset of Optimally Treated People With Long-Term Viral Suppression

Abstract: HIV genomes can be detected in CD133-sorted cells from a subset of donors with long-term viral suppression and, in most cases, cannot be explained by contamination with CD3(+) T cells.

Cited by 46 publications

References 29 publications

Vpr Overcomes Macrophage-Specific Restriction of HIV-1 Env Expression and Virion Production

Vpr Overcomes Macrophage-Specific Restriction of HIV-1 Env Expression and Virion Production

Pathogenesis and clinical implications of HIV-related anemia in 2013

Long-lived reservoirs of HIV-1

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