CD32a is a marker of a CD4 T-cell HIV reservoir harbouring replication-competent proviruses - PubMed (original) (raw)
. 2017 Mar 23;543(7646):564-567.
doi: 10.1038/nature21710. Epub 2017 Mar 15.
Gaël Petitjean 1, José-Luis López-Zaragoza 2 3 4, Timothée Bruel 2 5, Raoul Raffel 1, Christina Psomas 6, Jacques Reynes 6, Christine Lacabaratz 2 3 4, Yves Levy 2 3 4, Olivier Schwartz 2 5, Jean Daniel Lelievre 2 3 4, Monsef Benkirane 1
Affiliations
- PMID: 28297712
- DOI: 10.1038/nature21710
CD32a is a marker of a CD4 T-cell HIV reservoir harbouring replication-competent proviruses
Benjamin Descours et al. Nature. 2017.
Erratum in
- Corrigendum: CD32a is a marker of a CD4 T-cell HIV reservoir harbouring replication-competent proviruses.
Descours B, Petitjean G, López-Zaragoza JL, Bruel T, Raffel R, Psomas C, Reynes J, Lacabaratz C, Levy Y, Schwartz O, Daniel Lelievre J, Benkirane M. Descours B, et al. Nature. 2017 Jun 28;546(7660):686. doi: 10.1038/nature22807. Nature. 2017. PMID: 28658234
Abstract
The persistence of the HIV reservoir in infected individuals is a major obstacle to the development of a cure for HIV. Here, using an in vitro model of HIV-infected quiescent CD4 T cells, we reveal a gene expression signature of 103 upregulated genes that are specific for latently infected cells, including genes for 16 transmembrane proteins. In vitro screening for surface expression in HIV-infected quiescent CD4 T cells shows that the low-affinity receptor for the immunoglobulin G Fc fragment, CD32a, is the most highly induced, with no detectable expression in bystander cells. Notably, productive HIV-1 infection of T-cell-receptor-stimulated CD4 T cells is not associated with CD32a expression, suggesting that a quiescence-dependent mechanism is required for its induction. Using blood samples from HIV-1-positive participants receiving suppressive antiretroviral therapy, we identify a subpopulation of 0.012% of CD4 T cells that express CD32a and host up to three copies of HIV DNA per cell. This CD32a+ reservoir was highly enriched in inducible replication-competent proviruses and can be predominant in some participants. Our discovery that CD32a+ lymphocytes represent the elusive HIV-1 reservoir may lead to insights that will facilitate the specific targeting and elimination of this reservoir.
Comment in
- HIV: Finding latent needles in a haystack.
Richman DD. Richman DD. Nature. 2017 Mar 23;543(7646):499-500. doi: 10.1038/nature21899. Epub 2017 Mar 15. Nature. 2017. PMID: 28297707 No abstract available. - Hunting Down the HIV-1 Reservoir: A Starring Role for Antibodies?
Mouquet H. Mouquet H. Immunity. 2017 Apr 18;46(4):527-529. doi: 10.1016/j.immuni.2017.04.001. Immunity. 2017. PMID: 28423333 - Signature of the Sleeper Cell: A Biomarker of HIV Latency Revealed.
Pillai SK, Deeks SG. Pillai SK, et al. Trends Immunol. 2017 Jul;38(7):457-458. doi: 10.1016/j.it.2017.04.007. Epub 2017 May 13. Trends Immunol. 2017. PMID: 28511815 Free PMC article. - The role of CD32 during HIV-1 infection.
Bertagnolli LN, White JA, Simonetti FR, Beg SA, Lai J, Tomescu C, Murray AJ, Antar AAR, Zhang H, Margolick JB, Hoh R, Deeks SG, Tebas P, Montaner LJ, Siliciano RF, Laird GM, Siliciano JD. Bertagnolli LN, et al. Nature. 2018 Sep;561(7723):E17-E19. doi: 10.1038/s41586-018-0494-3. Epub 2018 Sep 19. Nature. 2018. PMID: 30232425 Free PMC article.
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