Date Published:
2023 Jan

Publication Type:
Journal Article

Authors:

W.G. Branton
J.P. Fernandes
N. Mohammadzadeh
M.A.L. Doan
J.D. Laman
B.B. Gelman
Z. Fagrouch
I. Kondova
P. Mooij
G. Koopman
C. Power

Secondary:
Brain Behav Immun

Volume:
107

Pagination:
110-123

PMID:
36202168

URL:
https://pubmed.ncbi.nlm.nih.gov/36202168

DOI:
10.1016/j.bbi.2022.09.019

Keywords:
Brain;HIV;HIV Infections;Humans;neurocognitive disorders;Neuroinflammatory Diseases;Receptors, CCR5

Abstract:
<p>BACKGROUND: Systemic inflammation accompanies HIV-1 infection, resulting in microbial translocation from different tissues. We investigated interactions between lentivirus infections, neuroinflammation and microbial molecule presence in the brain.METHODS: Brain tissues from adult humans with (n = 22) and without HIV-1 (n = 11) infection as well as adult nonhuman primates (NHPs) with (n = 11) and without (n = 4) SIV infection were investigated by RT-PCR/ddPCR, immunofluorescence and western blotting. Studies of viral infectivity, host immune gene expression and viability were performed in primary human neural cells.FINDINGS: Among NHPs, SIV DNA quantitation in brain showed increased levels among animals with SIV encephalitis (n = 5) that was associated with bacterial genomic copy number as well as CCR5 and CASP1 expression in brain. Microbial DnaK and peptidoglycan were immunodetected in brains from uninfected and SIV-infected animals, chiefly in glial cells. Human microglia infected by HIV-1 showed increased p24 production after exposure to peptidoglycan that was associated CCR5 induction. HIV-1 Vpr application to human neurons followed by peptidoglycan exposure resulted in reduced mitochondrial function and diminished beta-III tubulin expression. In human brains, bacterial genome copies (250-550 copies/gm of tissue), were correlated with increased bacterial rRNA and GroEL transcript levels in patients with HIV-associated neurocognitive disorders (HAND). Glial cells displayed microbial GroEL and peptidoglycan immunoreactivity accompanied by CCR5 induction in brains from patients with HAND.INTERPRETATION: Increased microbial genomes and proteins were evident in brain tissues from lentivirus-infected humans and animals and associated with neurological disease. Microbial molecule translocation into the brain might exacerbate neuroinflammatory disease severity and represent a driver of lentivirus-associated brain disease.</p>