Persistence of intact HIV-1 proviruses in the brain during suppressive antiretroviral therapy.
Weiwei SunYelizaveta RassadkinaCe GaoSarah Isabel CollensXiaodong LianIsaac H SolomonShibani S MukerjiXu G YuMathias LichterfeldPublished in: bioRxiv : the preprint server for biology (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 central nervous system (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 infected patients
- hiv aids
- induced apoptosis
- gene expression
- cell cycle arrest
- white matter
- blood brain barrier
- peripheral blood
- lymph node
- signaling pathway
- hepatitis c virus
- multiple sclerosis
- brain injury
- cell proliferation
- copy number
- cerebrospinal fluid
- deep brain stimulation
- sentinel lymph node
- cerebral ischemia
- genetic diversity
- cell free