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- Title
Persistence of intact HIV-1 proviruses in the brain during antiretroviral therapy.
- Authors
Weiwei Sun; Rassadkina, Yelizaveta; Ce Gao; Collens, Sarah Isabel; Xiaodong Lian; Solomon, Isaac H.; Mukerji, Shibani S.; Yu, Xu G.; Lichterfeld, Mathias
- Abstract
HIV-1 reservoir cells that circulate in peripheral blood during suppressive antiretroviral therapy (ART) have been well characterized, but little is known about the dissemination of HIV-1-infected cells across multiple anatomical tissues, especially the CNS. Here, we performed single-genome, near full-length HIV-1 next-generation sequencing to evaluate the proviral landscape in distinct anatomical compartments, including multiple CNS tissues, from 3 ART-treated participants at autopsy. While lymph nodes and, to a lesser extent, gastrointestinal and genitourinary tissues represented tissue hotspots for the persistence of intact proviruses, we also observed intact proviruses in CNS tissue sections, particularly in the basal ganglia. Multi-compartment dissemination of clonal intact and defective proviral sequences occurred across multiple anatomical tissues, including the CNS, and evidence for the clonal proliferation of HIV-1-infected cells was found in the basal ganglia, in the frontal lobe, in the thalamus and in periventricular white matter. Deep analysis of HIV-1 reservoirs in distinct tissues will be informative for advancing HIV-1 cure strategies.
- Subjects
ANTIRETROVIRAL agents; HIV; BASAL ganglia; WHITE matter (Nerve tissue); FRONTAL lobe; NUCLEOTIDE sequencing; AUTOPSY; HUMAN reproductive technology
- Publication
eLife, 2023, p1
- ISSN
2050-084X
- Publication type
Article
- DOI
10.7554/eLife.89837