HIV persistence: clonal expansion of cells in the latent reservoir

Kwon, Kyungyoon J.; Siliciano, Robert F.

doi:10.1172/jci95329

Cited by 25 publications

(21 citation statements)

References 25 publications

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“…The size of the latent reservoir remains relatively constant over time, with a calculated half_life of 3.6 years (Crooks et al, 2015; Finzi et al, 1999). However, the discovery of replication_ competent clones suggested a dynamic reservoir (Cohn and Nussenzweig, 2017; Kwon and Siliciano, 2017), and clones of T cells bearing integrated viruses have been reported to expand and contract over periods of years (Cohn et al, 2015; Wang et al, 2018). Expression of viral env in individuals on suppressive ART is limited, and neither 3BNC117 nor VRC01 (Lynch et al, 2015) infusion altered the size of the HIV reservoir in this setting.…”

Section: Discussionmentioning

confidence: 99%

Analysis of HIV-1 latent reservoir and rebound viruses in a clinical trial of anti-HIV-1 antibody 3BNC117

Cohen

Lorenzi

Krassnig

et al. 2018

Preprint

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SummaryIn the setting of a clinical trial evaluating the anti-HIV-1 antibody 3BNC117, Cohen et al. demonstrate that rebound viruses that emerge following interruption of antiretroviral therapy are distinct from circulating latent viruses. However, rebound viruses often appear to be recombinants between isolated latent viruses. By incorporating the possibility of recombination, 63% of the rebound viruses could have derived from the observed latent reservoir. In conclusion, viruses emerging during ATI in individuals treated with 3BNC117 are not the dominant species found in the circulating reservoir, but instead appear to represent recombinants. AbstractAll rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.

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Section: Discussionmentioning

confidence: 99%

Analysis of HIV-1 latent reservoir and rebound viruses in a clinical trial of anti-HIV-1 antibody 3BNC117

Cohen

Lorenzi

Krassnig

et al. 2018

Preprint

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“…HIV sequence analysis HIV sequence analysis DNA was prepared from PBMC and tissue samples, and HIV DNA copy numbers were determined using realtime polymerase chain reaction assays as previously described; in parallel, total cell equivalents were determined for each sample by quantifying CCR5 gene DNA copy number (45). In plasma samples, HIV RNA was extracted as previously described (10,27).…”

Section: Study Participantsmentioning

confidence: 99%

No evidence of ongoing HIV replication or compartmentalization in tissues during combination antiretroviral therapy: Implications for HIV eradication

et al. 2019

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HIV persistence during combination antiretroviral therapy (cART) is the principal obstacle to cure. Mechanisms responsible for persistence remain uncertain; infections may be maintained by persistence and clonal expansion of infected cells or by ongoing replication in anatomic locations with poor antiretroviral penetration. These mechanisms require different strategies for eradication, and determining their contributions to HIV persistence is essential. We used phylogenetic approaches to investigate, at the DNA level, HIV populations in blood, lymphoid, and other infected tissues obtained at colonoscopy or autopsy in individuals who were on cART for 8 to 16 years. We found no evidence of ongoing replication or compartmentalization of HIV; we did detect clonal expansion of infected cells that were present before cART. Long-term persistence, and not ongoing replication, is primarily responsible for maintaining HIV. HIV-infected cells present when cART is initiated represent the only identifiable source of persistence and is the appropriate focus for eradication.

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“…This results from a reshaping of the initial integration site bias in acute HIV-1 infection, which is determined by a number of genetic, epigenetic and mechanistic features [8,85]. Second, a subset of proviral integration sites observed in chronic HIV-1 infection appears linked to clonal expansion of the targeted cell [81][82][83][86][87][88]. Such clonally expanded cells have been found to carry intact as well as defective proviral sequences and appear to be present in most studied cases of HIV-infected individuals on cART [86,[89][90][91].…”

Section: The Contribution Of Ncrnas To Hiv-1 Latencymentioning

confidence: 99%

“…The mechanisms underlying clonal expansion are to date elusive. Expansion mediated by antigen-and cytokine-driven proliferation, a well-known phenomenon in T cell biology, has been discussed [8,87,92]. Alternatively, there is increasing evidence that the genomic locus at the proviral integration site and hence a functional proviral/human DNA crosstalk could play a dominant role.…”

Section: The Contribution Of Ncrnas To Hiv-1 Latencymentioning

confidence: 99%

“…Chimeric proviral/ human transcripts that arise from exaptation of the HIV-1 LTR promoter region for transcription of human endogenous gene products have indeed be observed [89,100]. In this way, proviral-derived DNA impacts on the host cell transcriptome and influences host cell physiology and behaviour such as differentiation, proliferation and/or survival and thereby stimulates expansion of the host cell clone [8,82,83,85,87]. This scenario could also explain observed clonal proliferation of cells with largely defective proviruses and solo-LTRs that are transcription/translation incompetent, cannot elicit immune responses and therefore are unlikely to undergo antigen-driven expansion [6,81].…”

Section: The Contribution Of Ncrnas To Hiv-1 Latencymentioning

confidence: 99%

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Epigenetic crosstalk in chronic infection with HIV-1

et al. 2020

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Human immunodeficiency virus 1 (HIV-1) replicates through the integration of its viral DNA into the genome of human immune target cells. Chronically infected individuals thus carry a genomic burden of virus-derived sequences that persists through antiretroviral therapy. This burden consists of a small fraction of intact, but transcriptionally silenced, i.e. latent, viral genomes and a dominant fraction of defective sequences. Remarkably, all viral-derived sequences are subject to interaction with host cellular physiology at various levels. In this review, we focus on epigenetic aspects of this interaction. We provide a comprehensive overview of how epigenetic mechanisms contribute to establishment and maintenance of HIV-1 gene repression during latency. We furthermore summarize findings indicating that HIV-1 infection leads to changes in the epigenome of target and bystander immune cells. Finally, we discuss how an improved understanding of epigenetic features and mechanisms involved in HIV-1 infection could be exploited for clinical use.

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HIV persistence: clonal expansion of cells in the latent reservoir

Cited by 25 publications

References 25 publications

Analysis of HIV-1 latent reservoir and rebound viruses in a clinical trial of anti-HIV-1 antibody 3BNC117

Analysis of HIV-1 latent reservoir and rebound viruses in a clinical trial of anti-HIV-1 antibody 3BNC117

No evidence of ongoing HIV replication or compartmentalization in tissues during combination antiretroviral therapy: Implications for HIV eradication

Epigenetic crosstalk in chronic infection with HIV-1

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