T FH in HIV Latency and as Sources of Replication-Competent Virus

Brodie, MJ; Connick, Elizabeth

doi:10.1016/j.tim.2016.02.006

Cited by 46 publications

(48 citation statements)

References 76 publications

(106 reference statements)

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“…Resting memory CD4+ T cell reservoirs have been estimated to have a half-life of 44 months, meaning that their clearance during ART may take as long as 73 years [13, 17, 18]. Subsequently, distinct populations of CD4+ T cells have also been recognized to contribute to the pool of latently infected cells [19–21], although those are outside the scope of the present review. The half-life of resting memory CD4+ T cell reservoirs corresponds to the long-phase decay of residual plasma viremia in persons taking long-term ART [22].…”

Section: Usual and Unusual Suspectsmentioning

confidence: 99%

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Are T cells the only HIV-1 reservoir?

2016

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Current antiretroviral therapies have improved the duration and quality of life of people living with HIV-1. However, viral reservoirs impede complete eradication of the virus. Although there are many strategies to eliminate infectious virus, the most actively pursued are latency reversing agents in conjunction with immune modulation. This strategy, known as “shock and kill”, has been tested primarily against the most widely recognized HIV-1 latent reservoir found in resting memory CD4+ T cells. This is in part because of the dearth of conclusive evidence about the existence of non-T cell reservoirs. Studies of non-T cell reservoirs have been difficult to interpret because of technical and biological issues that have hampered a better understanding. This review considers the current knowledge of non-T cell reservoirs, the challenges encountered in a better understanding of these populations, and their implications for HIV-1 cure research.

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Section: Usual and Unusual Suspectsmentioning

confidence: 99%

“…FDCs transfer antigens in the B cell follicles of all secondary lymphoid tissues, and in the process may transfer HIV-1 to T follicular helper cells that are also present in the B cell follicles [21]. …”

Section: Usual and Unusual Suspectsmentioning

confidence: 99%

Are T cells the only HIV-1 reservoir?

2016

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“…Evidence thus far is conflicting regarding productive infection of dendritic cells in vivo [29,30,54,63], although multiple studies support productive FIV infection of cultivated dendritic cells [43,63,64]. Likewise, reports may demonstrate productive HIV-1 infection of dendritic cells in vitro [65], but in vivo analyses suggest that extracellular virions bound to the cell surface of dendritic cells are the primary mode by which these cells transmit virus infection to CD4 T cells [13,66]. Evidence for productive replication of other subsets such as CD8+ T cells and B cells in vivo or in vitro has not been reported.…”

Section: Cell Reservoirs Of Fivmentioning

confidence: 99%

Central and peripheral reservoirs of feline immunodeficiency virus in cats: a review

Eckstrand

Sparger

Murphy

2017

Journal of General Virology

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Infection with feline immunodeficiency virus (FIV), a lentivirus similar to human immunodeficiency virus (HIV), results in lifelong viral persistence and progressive immunopathology in the cat. FIV has the ability to infect and produce infectious virus in a number of different cell types. FIV provirus can also be maintained in a replication-competent but transcriptionally quiescent state, facilitating viral persistence over time. Immediately after the initial infection, FIV infection quickly disseminates to many anatomical compartments within the host including lymphoid organs, gastrointestinal tract and brain. Collectively, the anatomic and cellular compartments that harbour FIV provirus constitute the viral reservoir and contain foci of both ongoing viral replication and transcriptionally restricted virus that may persist over time. The relative importance of the different phenotypes observed for infected cells, anatomic compartment, replication status and size of the reservoir represent crucial areas of investigation for developing effective viral suppression and eradication therapies. In this review, we discuss what is currently known about FIV reservoirs, and emphasize the utility of the FIV-infected cat as a model for the HIV-infected human.

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“…Similarly, Tfh cell frequencies in gut biopsies did not differ from those observed in treated HIV‐1‐positive and ‐negative individuals . Importantly, Tfh cells form an important reservoir during HIV/SIV infection …”

Section: Tfh Cell Differentiation and Functions Are Altered During Himentioning

confidence: 81%

“…22 Importantly, Tfh cells form an important reservoir during HIV/SIV infection. 23 Expansion of Tfh cells in LNs from chronically HIV-1infected individuals correlates with the viraemia 13 and is associated with gammaglobulinaemia and skewing of Bcell phenotype. 12,13,16 Importantly, Tfh cells exhibit the highest levels of HIV-1/SIV DNA and RNA compared with other LN CD4 + T-cell subsets, 13,14,18,24 and replicative HIV-1 virions can be recovered from activated Tfh cells isolated from viraemic patients.…”

Section: Tfh Cell Differentiation and Functions Are Altered During Himentioning

confidence: 99%

From dendritic cells to B cells dysfunctions during HIV‐1 infection: T follicular helper cells at the crossroads

2017

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Summary T follicular helper (Tfh) cells are essential for B‐cell differentiation and the subsequent antibody responses. Their numbers and functions are altered during human and simian immunodeficiency virus (HIV/SIV) infections. In lymphoid tissues, Tfh cells are present in germinal centre, where they are the main source of replicative HIV‐1 and represent a major reservoir. Paradoxically, Tfh cell numbers are increased in chronically infected individuals. Understanding the fate of Tfh cells in the course of HIV‐1 infection is essential for the design of efficient strategies toward a protective HIV vaccine or a cure. The purpose of this review is to summarize the recent advance in our understanding of Tfh cell dynamics during HIV/SIV infection. In particular, to explore the possible causes of their expansion in lymphoid tissues by discussing the impact of HIV‐1 infection on dendritic cells, to identify the molecular players rendering Tfh cells highly susceptible to HIV‐1 infection, and to consider the contribution of regulatory follicular T cells in shaping Tfh cell functions.

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T FH in HIV Latency and as Sources of Replication-Competent Virus

Cited by 46 publications

References 76 publications

Are T cells the only HIV-1 reservoir?

Are T cells the only HIV-1 reservoir?

Central and peripheral reservoirs of feline immunodeficiency virus in cats: a review

From dendritic cells to B cells dysfunctions during HIV‐1 infection: T follicular helper cells at the crossroads

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