{"title":"Phenotyping Viral Reservoirs to Reveal HIV-1 Hiding Places.","authors":"Wenxuan Chen, Ben Berkhout, Alexander O Pasternak","doi":"10.1007/s11904-025-00723-6","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose of review: </strong>Despite suppressive antiretroviral therapy (ART), HIV-1 reservoirs persist in various cell types and tissues and reignite active replication if therapy is stopped. Persistence of the viral reservoirs in people with HIV-1 (PWH) is the main obstacle to achieving a cure. Identification and characterization of cellular and tissue HIV-1 reservoirs is thus central to the cure research. Here, we discuss emerging insights into the phenotype of HIV-1 reservoir cells.</p><p><strong>Recent findings: </strong>HIV-1 persists in multiple tissues, anatomic locations, and cell types. Although contributions of different CD4 + T-cell subsets to the HIV-1 reservoir are not equal, all subsets harbor a part of the viral reservoir. A number of putative cellular markers of the HIV-1 reservoir have been proposed, such as immune checkpoint molecules, integrins, and pro-survival factors. CD32a expression was shown to be associated with a very prominent enrichment in HIV-1 DNA, although this finding has been challenged. Recent technological advances allow unbiased single-cell phenotypic analyses of cells harbouring total or intact HIV-1 proviruses. A number of phenotypic markers have been reported by several independent studies to be enriched on HIV-1 reservoir cells. Expression of some of these markers could be mechanistically linked to the reservoir persistence, as they could for instance shield the reservoir cells from the immune recognition or promote their survival. However, so far no single phenotypic marker, or combination of markers, can effectively distinguish HIV-infected from uninfected cells or identify all reservoir cells.</p>","PeriodicalId":10930,"journal":{"name":"Current HIV/AIDS Reports","volume":"22 1","pages":"15"},"PeriodicalIF":3.7000,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794352/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current HIV/AIDS Reports","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11904-025-00723-6","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
引用次数: 0
Abstract
Purpose of review: Despite suppressive antiretroviral therapy (ART), HIV-1 reservoirs persist in various cell types and tissues and reignite active replication if therapy is stopped. Persistence of the viral reservoirs in people with HIV-1 (PWH) is the main obstacle to achieving a cure. Identification and characterization of cellular and tissue HIV-1 reservoirs is thus central to the cure research. Here, we discuss emerging insights into the phenotype of HIV-1 reservoir cells.
Recent findings: HIV-1 persists in multiple tissues, anatomic locations, and cell types. Although contributions of different CD4 + T-cell subsets to the HIV-1 reservoir are not equal, all subsets harbor a part of the viral reservoir. A number of putative cellular markers of the HIV-1 reservoir have been proposed, such as immune checkpoint molecules, integrins, and pro-survival factors. CD32a expression was shown to be associated with a very prominent enrichment in HIV-1 DNA, although this finding has been challenged. Recent technological advances allow unbiased single-cell phenotypic analyses of cells harbouring total or intact HIV-1 proviruses. A number of phenotypic markers have been reported by several independent studies to be enriched on HIV-1 reservoir cells. Expression of some of these markers could be mechanistically linked to the reservoir persistence, as they could for instance shield the reservoir cells from the immune recognition or promote their survival. However, so far no single phenotypic marker, or combination of markers, can effectively distinguish HIV-infected from uninfected cells or identify all reservoir cells.
期刊介绍:
This journal intends to provide clear, insightful, balanced contributions by international experts that review the most important, recently published clinical findings related to the diagnosis, treatment, management, and prevention of HIV/AIDS.
We accomplish this aim by appointing international authorities to serve as Section Editors in key subject areas, such as antiretroviral therapies, behavioral aspects of management, and metabolic complications and comorbidity. Section Editors, in turn, select topics for which leading experts contribute comprehensive review articles that emphasize new developments and recently published papers of major importance, highlighted by annotated reference lists. An international Editorial Board reviews the annual table of contents, suggests articles of special interest to their country/region, and ensures that topics are current and include emerging research. Commentaries from well-known figures in the field are also provided.