Meng Wang, Jennifer Yoon, Hailey Reisert, Bibhuprasad Das, Benjamin Orlinick, Jennifer Chiarella, Elias K Halvas, John Mellors, Alina Ps Pang, Lydia Aoun Barakat, Margaret Fikrig, Joshua Cyktor, Yuval Kluger, Serena Spudich, Michael J Corley, Shelli F Farhadian
JCI insight 2024 Apr 08The central nervous system HIV reservoir is incompletely understood and is a major barrier to HIV cure. We profiled people with HIV (PWH) and uninfected controls through single-cell transcriptomic and T cell receptor (TCR) sequencing to understand the dynamics of HIV persistence in the CNS. In PWH on ART, we found that most participants had single cells containing HIV-1 RNA, which was found predominantly in CD4 central memory T cells, in both cerebrospinal fluid (CSF) and blood. HIV-1 RNA-containing cells were found more frequently in CSF than blood, indicating a higher burden of reservoir cells in the CNS than blood for some PWH. Most CD4 T cell clones containing infected cells were compartment specific, while some (22%) - including rare clones with members of the clone containing detectable HIV RNA in both blood and CSF - were found in both CSF and blood. These results suggest that infected T cells trafficked between tissue compartments and that maintenance and expansion of infected T cell clones contributed to the CNS reservoir in PWH on ART.
Meng Wang, Jennifer Yoon, Hailey Reisert, Bibhuprasad Das, Benjamin Orlinick, Jennifer Chiarella, Elias K Halvas, John Mellors, Alina Ps Pang, Lydia Aoun Barakat, Margaret Fikrig, Joshua Cyktor, Yuval Kluger, Serena Spudich, Michael J Corley, Shelli F Farhadian. HIV-1-infected T cell clones are shared across cerebrospinal fluid and blood during ART. JCI insight. 2024 Apr 08;9(7)
PMID: 38587074
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