Persistence of intact HIV-1 proviruses in the brain during antiretroviral therapy.
Wei-Wei SunYelizaveta RassadkinaCe GaoSarah Isabel CollensXiaodong LianIsaac H SolomonShibani S MukerjiXu G YuMathias D LichterfeldPublished in: eLife (2023)
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.
Keyphrases
- antiretroviral therapy
- hiv infected
- hiv positive
- human immunodeficiency virus
- hiv aids
- hiv infected patients
- induced apoptosis
- gene expression
- white matter
- cell cycle arrest
- blood brain barrier
- lymph node
- peripheral blood
- signaling pathway
- endoplasmic reticulum stress
- multiple sclerosis
- oxidative stress
- hepatitis c virus
- pi k akt
- dna methylation
- genome wide
- early stage
- cell proliferation