Single-Cell Characterization of Viral Translation-Competent Reservoirs in HIV-Infected Individuals.

TitleSingle-Cell Characterization of Viral Translation-Competent Reservoirs in HIV-Infected Individuals.
Publication TypeJournal Article
Year of Publication2016
AuthorsBaxter AE, Niessl J, Fromentin R, Richard J, Porichis F, Charlebois R, Massanella M, Brassard N, Alsahafi N, Delgado G-G, Routy J-P, Walker BD, Finzi A, Chomont N, Kaufmann DE
JournalCell Host Microbe
Date Published09/14/2016

HIV cure efforts are hampered by limited characterization of the cells supporting HIV replication in vivo and inadequate methods for quantifying the latent viral reservoir in patients receiving antiretroviral therapy. We combine fluorescent in situ RNA hybridization with detection of HIV protein and flow cytometry, enabling detection of 0.5-1 gag-pol mRNA(+)/Gag protein(+)-infected cells per million. In the peripheral blood of untreated persons, active HIV replication correlated with viremia and occurred in CD4 T cells expressing T follicular helper cell markers and inhibitory co-receptors. In virally suppressed subjects, the approach identified latently infected cells capable of producing HIV mRNA and protein after stimulation with PMA/ionomycin and latency-reversing agents (LRAs). While ingenol-induced reactivation mirrored the effector and central/transitional memory CD4 T cell contribution to the pool of integrated HIV DNA, bryostatin-induced reactivation occurred predominantly in cells expressing effector memory markers. This indicates that CD4 T cell differentiation status differentially affects LRA effectiveness.

Alternate JournalCell Host Microbe
PubMed ID27545045
PubMed Central IDPMC5025389
Grant ListR01 HL092565 / HL / NHLBI NIH HHS / United States
UM1 AI100663 / AI / NIAID NIH HHS / United States
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