Replication-Competent Simian Immunodeficiency Virus (SIV) Gag Escape Mutations Archived in Latent Reservoirs during Antiretroviral Treatment of SIV-Infected Macaques

Se, Queen; Bm, Mears; Km, Kelly; Jl, Dorsey; Liao, Zhaohao; Jb, Dinoso; Gama, Lúcio; Rj, Adams; Zink, M. Christine; Je, Clements; Kent, Stephen J.; Jl, Mankowski

doi:10.1128/jvi.00366-11

Cited by 36 publications

(46 citation statements)

References 38 publications

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“…Recent advances in the implementation of fully effective ART in the non-human primate (NHP) SIV model system (see below) offer hope that this controversy will soon be resolved 76 , as extensive and conclusive tissue sampling of optimally treated animals should be possible. In addition, recently developed humanized mouse models of latent HIV-1 infection will address this question in the context of the human virus in human cells 77 .…”

Section: Cellular Reservoirs Of Hiv-1mentioning

confidence: 99%

Eradicating HIV-1 infection: seeking to clear a persistent pathogen

et al. 2014

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Effective antiretroviral therapy (ART) blunts viraemia, which enables HIV-1-infected individuals to control infection and live long, productive lives. However, HIV-1 infection remains incurable owing to the persistence of a viral reservoir that harbours integrated provirus within host cellular DNA. This latent infection is unaffected by ART and hidden from the immune system. Recent studies have focused on the development of therapies to disrupt latency. These efforts unmasked residual viral genomes and highlighted the need to enable the clearance of latently infected cells, perhaps via old and new strategies that improve the HIV-1-specific immune response. In this Review, we explore new approaches to eradicate established HIV-1 infection and avoid the burden of lifelong ART.

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Section: Cellular Reservoirs Of Hiv-1mentioning

confidence: 99%

Eradicating HIV-1 infection: seeking to clear a persistent pathogen

et al. 2014

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“…The topic of anatomical reservoirs of lentiviral persistence became particularly important with the advent of antiretroviral drug therapy (ART) for HIV-infected humans. While ART is highly effective for suppressing HIV viral replication, there is evidence that incomplete anatomically localized suppression of viral replication occurs due to inadequate tissue drug concentrations in particular anatomic sites such as the brain [86][87][88][89][90]. As is true for cellular reservoirs, technical challenges impede the identification of tissue reservoirs infected with replication-competent provirus.…”

Section: Fiv Tissue Reservoirsmentioning

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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“…Another important area is the use of animal models to recreate HIV-1 infection of the CNS and use these systems to dissect treatment outcomes following administration of HIV-1 eradication strategies [22,54-57]. Studies performed in infected macaques determined that treatment with cART for 6 months resulted in rapid suppression of viral replication in the blood and CSF but the level of SIV DNA in the brain did not change [56].…”

Section: The Critical Questions That Remain Unansweredmentioning

confidence: 99%

“…Studies performed in infected macaques determined that treatment with cART for 6 months resulted in rapid suppression of viral replication in the blood and CSF but the level of SIV DNA in the brain did not change [56]. Other studies in macaques suggest that immune escape variants may become archived in the brain and re-emerge following cessation of cART [57]. These models may be useful to analyze the establishment of latency and the CNS viral reservoir, because tissue samples can be readily accessed.…”

Section: The Critical Questions That Remain Unansweredmentioning

confidence: 99%

Is the central nervous system a reservoir of HIV-1?

Gray¹,

Roche²,

Flynn³

et al. 2014

Current Opinion in HIV and AIDS

108

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Purpose of the review To summarize the evidence in the literature that supports the CNS as a viral reservoir for HIV-1 and to prioritise future research efforts. Recent findings HIV-1 DNA has been detected in brain tissue of patients with undetectable viral load or neurocognitive disorders, and is associated with long-lived cells such as astrocytes and microglia. In neurocognitively normal patients, HIV-1 can be found at high frequency in these cells (4% of astrocytes and 20% of macrophages). CNS cells have unique molecular mechanisms to suppress viral replication and induce latency, which include increased expression of dominant negative transcription factors and suppressive epigenetic factors. There is also evidence of continued inflammation in patients lacking a CNS viral load, suggesting the production and activity of viral neurotoxins (for example Tat). Summary Together, these findings provide evidence that the CNS can potentially act as a viral reservoir of HIV-1. However, the majority of these studies were performed in historical cohorts (absence of cART or presence of viral load) which do not reflect modern day patients (cART-treated and undetectable viral load). Future studies will need to examine patient samples with these characteristics to conclusively determine if the CNS represents a relevant and important viral reservoir.

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Replication-Competent Simian Immunodeficiency Virus (SIV) Gag Escape Mutations Archived in Latent Reservoirs during Antiretroviral Treatment of SIV-Infected Macaques

Cited by 36 publications

References 38 publications

Eradicating HIV-1 infection: seeking to clear a persistent pathogen

Eradicating HIV-1 infection: seeking to clear a persistent pathogen

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

Is the central nervous system a reservoir of HIV-1?

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