|Title||Single-Cell Characterization of Viral Translation-Competent Reservoirs in HIV-Infected Individuals.|
|Publication Type||Journal Article|
|Year of Publication||2016|
|Authors||Baxter 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|
|Journal||Cell Host Microbe|
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 Journal||Cell Host Microbe|
|PubMed Central ID||PMC5025389|
|Grant List||R01 HL092565 / HL / NHLBI NIH HHS / United States |
UM1 AI100663 / AI / NIAID NIH HHS / United States
Single-Cell Characterization of Viral Translation-Competent Reservoirs in HIV-Infected Individuals.