دورية أكاديمية
أعرض في EDS

The largest HIV-1-infected T cell clones in children on long-term combination antiretroviral therapy contain solo LTRs.

التفاصيل البيبلوغرافية
العنوان: The largest HIV-1-infected T cell clones in children on long-term combination antiretroviral therapy contain solo LTRs.
المؤلفون: Botha JC; Stellenbosch University , Cape Town, South Africa., Demirov D; Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research , Frederick, Maryland, USA., Gordijn C; Stellenbosch University , Cape Town, South Africa., Katusiime MG; HIV Dynamics and Replication Program, National Cancer Institute , Frederick, Maryland, USA., Bale MJ; Laboratory of Epigenetics and Immunity, Department of Pathology and Laboratory Medicine, Weill Cornell Medicine , New York, New York, USA., Wu X; HIV Dynamics and Replication Program, National Cancer Institute , Frederick, Maryland, USA., Wells D; HIV Dynamics and Replication Program, National Cancer Institute , Frederick, Maryland, USA., Hughes SH; HIV Dynamics and Replication Program, National Cancer Institute , Frederick, Maryland, USA., Cotton MF; Stellenbosch University , Cape Town, South Africa., Mellors JW; Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania, USA., Kearney MF; HIV Dynamics and Replication Program, National Cancer Institute , Frederick, Maryland, USA., van Zyl GU; Stellenbosch University , Cape Town, South Africa.
المصدر: MBio [mBio] 2023 Aug 31; Vol. 14 (4), pp. e0111623. Date of Electronic Publication: 2023 Aug 02.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 101519231 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2150-7511 (Electronic) NLM ISO Abbreviation: mBio Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, D.C. : American Society for Microbiology
مواضيع طبية MeSH: HIV Infections*/drug therapy , HIV-1*/genetics , HIV Seropositivity*, Animals ; Antiretroviral Therapy, Highly Active ; Proviruses/genetics ; CD4-Positive T-Lymphocytes ; Clone Cells ; HIV Long Terminal Repeat
مستخلص: Combination antiretroviral therapy (cART) suppresses viral replication but does not cure HIV infection because a reservoir of infectious (intact) HIV proviruses persists in long-lived CD4+T cells. However, a large majority (>95%) of HIV-infected cells that persist on effective cART carry defective (non-infectious) proviruses. Defective proviruses consisting of only a single LTR (solo long terminal repeat) are commonly found as endogenous retroviruses in many animal species, but the frequency of solo-LTR HIV proviruses has not been well defined. Here we show that, in five pediatric donors whose viremia was suppressed on cART for at least 5 years, the proviruses in the nine largest clones of HIV-infected cells were solo LTRs. The sizes of five of these clones were assayed longitudinally by integration site-specific quantitative PCR. Minor waxing and waning of the clones was observed, suggesting that these clones are generally stable over time. Our findings show that solo LTRs comprise a large fraction of the proviruses in infected cell clones that persist in children on long-term cART. IMPORTANCE This work highlights that severely deleted HIV-1 proviruses comprise a significant proportion of the proviral landscape and are often overlooked.
Competing Interests: John W. Mellors reports additional research grant funding from USAID and Gilead Sciences, Inc., to the University of Pittsburgh; scientific advisory board member to Gilead Sciences, Inc.; shareholder in Abound Bio, Inc., and MingMed; and share option holder in Infectious Disease Connect.
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معلومات مُعتمدة: UM1 AI106701 United States AI NIAID NIH HHS; UM1 AI164565 United States AI NIAID NIH HHS; UM1 AI164556 United States AI NIAID NIH HHS; UM1 AI126603 United States AI NIAID NIH HHS; U01 CA200441 United States CA NCI NIH HHS; R01 AI165031 United States AI NIAID NIH HHS; 75N91019D00024 United States CA NCI NIH HHS
فهرسة مساهمة: Keywords: HIV; HIV cell clones; proviral quantification; provirus; solo LTR
تواريخ الأحداث: Date Created: 20230802 Date Completed: 20230904 Latest Revision: 20240302
رمز التحديث: 20240302
مُعرف محوري في PubMed: PMC10470503
DOI: 10.1128/mbio.01116-23
PMID: 37530525
قاعدة البيانات: MEDLINE
الوصف
تدمد:2150-7511
DOI:10.1128/mbio.01116-23