Date Published:
2024 July

Publication Type:
Journal Article

Authors:

Johannes Cm Schlachetzki
Sara Gianella
Zhengyu Ouyang
Addison J Lana
Xiaoxu Yang
Sydney O'Brien
Jean F Challacombe
Peter J Gaskill
Kelly L Jordan-Sciutto
Antoine Chaillon
David Moore
Cristian L Achim
Ronald J Ellis
Davey M Smith
Christopher K Glass

PMID:
39060113

URL:
https://pubmed.ncbi.nlm.nih.gov/39060113/

DOI:
10.26508/lsa.202402736

Abstract:
The presence of HIV in sequestered reservoirs is a central impediment to a functional cure, allowing HIV to persist despite life-long antiretroviral therapy (ART), and driving a variety of comorbid conditions. Our understanding of the latent HIV reservoir in the central nervous system is incomplete, because of difficulties in accessing human central nervous system tissues. Microglia contribute to HIV reservoirs, but the molecular phenotype of HIV-infected microglia is poorly understood. We leveraged the unique "Last Gift" rapid autopsy program, in which people with HIV are closely followed until days or even hours before death. Microglial populations were heterogeneous regarding their gene expression profiles but showed similar chromatin accessibility landscapes. Despite ART, we detected occasional microglia containing cell-associated HIV RNA and HIV DNA integrated into open regions of the host's genome (∼0.005%). Microglia with detectable HIV RNA showed an inflammatory phenotype. These results demonstrate a distinct myeloid cell reservoir in the brains of people with HIV despite suppressive ART. Strategies for curing HIV and neurocognitive impairment will need to consider the myeloid compartment to be successful.