pr401117m_si_002.xlsx (44.85 kB)
Identification of Nitrated Immunoglobulin Variable Regions in the HIV-Infected Human Brain: Implications in HIV Infection and Immune Response
dataset
posted on 2015-12-17, 04:13 authored by Lerna Uzasci, Mario A. Bianchet, Robert
J. Cotter, Avindra NathHIV can infiltrate the brain and lead to HIV-associated neurocognitive
disorders (HAND). The pathophysiology of HAND is poorly understood,
and there are no diagnostic biomarkers for it. Previously, an increase
in inducible nitric oxide synthase levels and protein tyrosine nitration
in the brain were found to correlate with the severity of HAND., In this study, we analyzed human brains from individuals who had
HIV infection without encephalitis and with encephalitis/HAND and
compared them to the brains of healthy individuals. We identified
the nitrated proteins and determined the sites of modification using
affinity enrichment followed by high-resolution and high-mass-accuracy
nanoLC–MS/MS. We found that nitrated proteins were predominantly
present in the HIV-infected individuals with encephalitis, and, interestingly,
the modifications were predominantly located on immunoglobulin variable
regions. Our molecular model indicated potential interactions with
HIV envelope proteins and changes on the heavy and light chain interface
upon the nitration and nitrohydroxylation of these residues. Therefore,
our findings suggest a role for these modifications in the immune
response, which may have implications in disease pathogenesis.