Abstract
HIV-1 Tat is an important regulatory protein involved in AIDS pathogenesis. However, the immunoprofiles of anti-Tat responses remain unclear. We analysed the immunoprofiles of the anti-Tat antibody responses and the neutralizing activities. Out of 326 HIV-1-seropositive individuals, 12.9% were positive for anti-Tat antibodies. We found six different immunological profiles of anti-Tat antibody responses: full-potential response, combined response, N-specific response, C-specific response, full-length Tat-specific response and Tat-related response. These responses represent two types of anti-Tat responses: the major complete response and the alternative C-prone response. A Tat-neutralizing activity is significantly higher in anti-Tat-seropositive samples than anti-Tat-negative or healthy blood-donor samples, and significantly correlates with the anti-Tat reactivities. The data here could contribute to a better understanding of the significance of anti-Tat responses in preventing HIV pathogenesis and could be useful for designing more effective vaccines in the future.
Highlights
As one of the six accessory proteins of HIV-1, Tat is synthesized during both the early and late stages of viral replication and is critical for these processes
The Tat protein can be divided into six functional domains[1,2]: (1) the N-terminal acidic aa region, which has been linked to Tat immunosuppressive activity[3,4,5,6]; (2) the cysteine-rich region, which is responsible for transactivation of transcription; (3) the ‘‘core’’ region, which is highly conserved; (4) the basic region, which recognizes the transactivation response element (TAR) [7]and plays important roles in both the nuclear localization of Tat [8] and the entry of extracellular Tat into bystander cells[9]; (5) the glutamine-rich region, which has the highest rate of sequence variation; and (6) the C-terminal region, which is encoded by the second exon and contains the ‘‘RGD’’ motif that allows Tat to bind integrin [10,11]
Tat is actively released from HIV-1-infected cells [10,11] and acts as an extra-cellular toxin [12], which plays a crucial role in HIV-1 pathogenesis, including development of HIV-associated dementia, HIV-related opportunistic infections and Kaposi’s sarcoma
Summary
As one of the six accessory proteins of HIV-1, Tat is synthesized during both the early and late stages of viral replication and is critical for these processes. Previous studies have shown that approximately 20% of infected individuals produce detectable amounts of Tat-specific antibodies, and the presence of anti-Tat antibodies is strongly correlated with slower disease progression and that no AIDS events were observed in persistently anti-Tat-seropositive subjects[13,14,15,16,17]. These results strongly suggest that Tat is a promising target for the development of both preventive and therapeutic vaccines [18,19]. Our findings provide a novel source of information with respect to anti-Tat responses and Tat-neutralizing potential that should be very important for understanding the role of this response in the prevention of HIV pathogenesis and vaccine design
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