Antibodies against HIV Tat are associated with protection against dopaminergic neuronal dysfunctions but are scantily produced in people living with HIV 2640

Abstract Description Tat is a transactivator of HIV transcription that can be secreted and affect uninfected cells. In the nervous system, deleterious effects of extracellular Tat have been linked to HIV-associated neurocognitive disorders (HAND), which include motor and gait abnormalities associated with dopaminergic neuronal dysfunctions that share similarities to Parkinson’s disease. Tat has been reported to impair dopaminergic neuronal cells and reduce dopamine release. This study examined the potential protective role of anti-Tat antibodies. In contrast to the robust antibody responses to Env, Gag, and Nef, minimal responses were elicited against Tat during early and chronic infection. However, among 42 individuals with HIV and a spectrum of neurological abnormalities, serum IgG levels to Tat were inversely associated with severity of extrapyramidal motor abnormalities as measured by the Unified Parkinson’s Disease Rating Scale (UPDRS). Levels of anti-Tat IgG were lower in subjects with more severe deficits (UPDRS scores of ≥ 10). The association was observed specifically with IgG against the conserved, pathogenic cysteine-rich region of Tat. We also evaluated the effects of antibodies on Tat-induced transactivation. Sera from people with HIV mediated no inhibition, while serum IgG from Tat-immunized rabbits exhibited a potent blocking activity. These data provide initial evidence to support the idea for a therapeutic Tat vaccine to mitigate HIV-associated dopaminergic neurodegeneration. Funding Sources Supported by US VA Research Career Scientist Award; NIH T32 Training Grant; NIH U24MH100931; NIH 75N95023C00015; NIH RO1NS108801; NIH Y1-AI-5072; US DoD IDCRP-000-05;, US DoD HU0001190002. Topic Categories Viral Immunology (VIR)