New research shows HIV can lie dormant in the brain jclinicalinvest
). We also accessed brain tissue through the NDRI. With these brain tissues from both PWH and people without HIV, we achieved successful isolation and ex vivo culturing of MG, principally TEME119MG. In addition, we observed that brain-derived MG may proliferate ex vivo, which may enhance the ability to study these cells. We were thus able to examine the role of MG as stable reservoirs of persistent HIV infection in the CNS.
To ensure that replication-competent HIV was truly derived from brain MG, we first used highly sensitive RT-qPCR and ddPCR assays with the detection limit of 1 T cell per million MG. Our data showed that RNA for the T cell marker CD3 was undetectable in isolated MG. Of note, in our virological studies, we assessed fewer than 1 million MG per culture, ensuring that there was likely to be less than 1 T cell in our purified MG during our reservoir assay.
It has been reported that T cells in the brain may provide an HIV reservoir in an HIV-infected Hu mouse model of HIV latency . Unfortunately, we were unable to isolate a sufficient number of T cells from brain tissues from each person with HIV to determine whether they contained HIV. Since CD3T cells within the isolated CNS T cells might impair viral outgrowth.
Our analysis revealed that during suppressive ART, the basal levels of cell-associated viral RNA were very low in brain MG isolated either from NHPs or humans. Importantly, SIV RNA was up to 6-fold lower than SIV DNA levels in NHP brain MG, while HIV RNA was up to 33-fold lower than HIV DNA levels in human MG. These observations suggest that proviral HIV in the brain MG is largely silent in PWH on ART.
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