Tat-specific antibodies associated with better HIV-associated motor function

Tat is a transactivator of HIV transcription that can be secreted to affect nearby cells. Deleterious central nervous system effects of extracellular Tat include dopaminergic neuron dysfunction, raising the possibility that Tat secretion may be linked to Parkinsonian motor features seen in people with HIV (PWH). This study examined the potential association of anti-Tat antibodies and extrapyramidal motor dysfunction in PWH. In 42 PWH who were chronically infected and characterized for neurological abnormalities, anti-Tat IgG levels were lower in individuals with more severe extrapyramidal motor abnormalities as measured by the Unified Parkinson's Disease Rating Scale (UPDRS). The association was observed specifically with IgG against the cysteine-rich Tat region. However, the IgG responses to Tat were weak in comparison to responses against the other HIV antigens. This disparity was evident in plasma and cerebrospinal fluid, and was also seen in early infection, before antiretroviral therapy. When the effects of antibodies on Tat function were evaluated, PWH plasma had no activity against Tat-induced transactivation, while Tat-immunized mouse and rabbit sera exhibited a potent inhibitory activity. These data provide initial evidence for a protective potential of anti-Tat antibodies and raise the possibility that a therapeutic Tat vaccine might alleviate clinical signs of HIV-associated dopaminergic dysfunction.