» Articles » PMID: 36804957

HIV Rapidly Targets a Diverse Pool of CD4 T cells to Establish Productive and Latent Infections

Abstract

Upon infection, HIV disseminates throughout the human body within 1-2 weeks. However, its early cellular targets remain poorly characterized. We used a single-cell approach to retrieve the phenotype and TCR sequence of infected cells in blood and lymphoid tissue from individuals at the earliest stages of HIV infection. HIV initially targeted a few proliferating memory CD4 T cells displaying high surface expression of CCR5. The phenotype of productively infected cells differed by Fiebig stage and between blood and lymph nodes. The TCR repertoire of productively infected cells was heavily biased, with preferential infection of previously expanded and disseminated clones, but composed almost exclusively of unique clonotypes, indicating that they were the product of independent infection events. Latent genetically intact proviruses were already archived early in infection. Hence, productive infection is initially established in a pool of phenotypically and clonotypically distinct T cells, and latently infected cells are generated simultaneously.

Citing Articles

Blood and tissue HIV-1 reservoirs display plasticity and lack of compartmentalization in virally suppressed people.

Pardons M, Lambrechts L, Noppe Y, Termote L, De Braekeleer S, Vega J Nat Commun. 2025; 16(1):2173.

PMID: 40038305 PMC: 11880387. DOI: 10.1038/s41467-025-57332-5.


Differences in HIV-1 reservoir size, landscape characteristics, and decay dynamics in acute and chronic treated HIV-1 Clade C infection.

Reddy K, Lee G, Reddy N, Chikowore T, Baisley K, Dong K Elife. 2025; 13.

PMID: 39976231 PMC: 11841988. DOI: 10.7554/eLife.96617.


Barcoded HIV-1 reveals viral persistence driven by clonal proliferation and distinct epigenetic patterns.

Zhang T, Shi Y, Komarova N, Wordaz D, Kostelny M, Gonzales A Nat Commun. 2025; 16(1):1641.

PMID: 39952916 PMC: 11829055. DOI: 10.1038/s41467-025-56771-4.


A simple phylogenetic approach to analyze hypermutated HIV proviruses reveals insights into their dynamics and persistence during antiretroviral therapy.

Shahid A, Jones B, Duncan M, MacLennan S, Dapp M, Kuniholm M Virus Evol. 2025; 11(1):veae094.

PMID: 39802824 PMC: 11724191. DOI: 10.1093/ve/veae094.


Cognate antigen engagement induces HIV-1 expression in latently infected CD4 T cells from people on long-term antiretroviral therapy.

Moskovljevic M, Dragoni F, Board N, Wu F, Lai J, Zhang H Immunity. 2024; 57(12):2928-2944.e6.

PMID: 39612916 PMC: 11896817. DOI: 10.1016/j.immuni.2024.11.002.


References
1.
Mitchell J, Pollara J, Dietze K, Edwards R, Nohara J, Nguessan K . Anti-HIV antibody development up to 1 year after antiretroviral therapy initiation in acute HIV infection. J Clin Invest. 2021; 132(1). PMC: 8718150. DOI: 10.1172/JCI150937. View

2.
Ananworanich J, Fletcher J, Pinyakorn S, van Griensven F, Vandergeeten C, Schuetz A . A novel acute HIV infection staging system based on 4th generation immunoassay. Retrovirology. 2013; 10:56. PMC: 3669623. DOI: 10.1186/1742-4690-10-56. View

3.
Leyre L, Kroon E, Vandergeeten C, Sacdalan C, Colby D, Buranapraditkun S . Abundant HIV-infected cells in blood and tissues are rapidly cleared upon ART initiation during acute HIV infection. Sci Transl Med. 2020; 12(533). PMC: 7293182. DOI: 10.1126/scitranslmed.aav3491. View

4.
Schacker T, Little S, Connick E, GEBHARD K, Zhang Z, Krieger J . Productive infection of T cells in lymphoid tissues during primary and early human immunodeficiency virus infection. J Infect Dis. 2001; 183(4):555-62. DOI: 10.1086/318524. View

5.
Pinzone M, VanBelzen D, Weissman S, Bertuccio M, Cannon L, Venanzi-Rullo E . Longitudinal HIV sequencing reveals reservoir expression leading to decay which is obscured by clonal expansion. Nat Commun. 2019; 10(1):728. PMC: 6374386. DOI: 10.1038/s41467-019-08431-7. View