The human immunodeficiency virus Tat regulatory protein is essential for virus replication and for the efficient transcription of HIV-1 provirus, and in the pathogenesis of AIDS. The role of the tat gene was investigated in 300 samples. It was found that 71.7% were subtype CRF_01AE, 9.3% were subtype B, while 11.7 and 7.3% of them were cross-reactive and non-typeable, respectively. Moreover the results from peptide ELISA also showed that a low CD4 cell count was related to a low anti-Tat antibody (p < 0.05), which may be due to the progression of HIV-1, which can be found predominantly in AIDS patients. The results of nested PCR showed that the second Tat exon might also play a role in T-cell activation. Reverse transcription polymerase chain reaction (RT-PCR) was used to measure HIV-1 mRNA expression in PBMC. RT-PCR negative results were found mostly in the asymptomatic HIV-seropositive group (88%). HIV-1 mRNA expression was found to correlate with current immunologic status. The differences in Tat protein sequences from DNA sequencing between the patients who had anti-Tat antibody positive and anti-Tat antibody negative, were not significant (p > 0.05). These results suggested that the Tat amino acid sequences were conserved among each group of samples and did not change significantly compared with the consensus sequence in previous studies. Several factors make Tat an attractive target for vaccine design.
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Expert Rev Vaccines
September 2022
National HIV/AIDS Research Center, Istituto Superiore Di Sanità, Rome, Italy.
Introduction: Upon the introduction of the combination antiretroviral therapy (cART), HIV infection has become a chronic disease. However, cART is unable to eradicate the virus and fails to restore the CD4 counts in about 30% of the treated individuals. Furthermore, treatment is life-long, and it does not protect from morbidities typically observed in the elderly.
View Article and Find Full Text PDFInt J Mol Sci
February 2022
National HIV/AIDS Research Center, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Kaposi's sarcoma (KS) is an angioproliferative tumor showing an increased frequency and aggressiveness in HIV-infected subjects (AIDS-KS), due to the combined effects of inflammatory cytokines (IC), angiogenic factors, and the HIV-1 Tat protein. While the introduction of effective combined antiretroviral regimens greatly improved AIDS-KS incidence and course, it continues to be an incurable disease and the development of new rational targeted therapies is warranted. We used the BKV/Tat transgenic mouse model to evaluate the effects of IC and anti-Tat antibodies (Abs) treatment on KS-like lesions arising in BKV/Tat mice.
View Article and Find Full Text PDFEBioMedicine
April 2021
National HIV/AIDS Research Center, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome 00161, Italy. Electronic address:
Background: Low-level HIV viremia originating from virus reactivation in HIV reservoirs is often present in cART treated individuals and represents a persisting source of immune stimulation associated with sub-optimal recovery of CD4 T cells. The HIV-1 Tat protein is released in the extracellular milieu and activates immune cells and latent HIV, leading to virus production and release. However, the relation of anti-Tat immunity with residual viremia, persistent immune activation and CD4 T-cell dynamics has not yet been defined.
View Article and Find Full Text PDFViruses
April 2020
Department of Cell and Molecular Biology, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia.
The human immunodeficiency virus type 1 (HIV) establishes a chronic infection that can be well controlled, but not cured, by combined antiretroviral therapy (cART). Interventions have been explored to accomplish a functional cure, meaning that a patient remains infected but HIV is undetectable in the blood, with the aim of allowing patients to live without cART. Tat, the viral transactivator of transcription protein, plays a critical role in controlling HIV transcription, latency, and viral rebound following the interruption of cART treatment.
View Article and Find Full Text PDFExpert Rev Vaccines
January 2020
National HIV/AIDS Research Center, Istituto Superiore di Sanità, Rome, Italy.
: Although successful at suppressing HIV replication, combination antiretroviral therapy (cART) only partially restores immune functions and fails to reduce the latent HIV reservoir, thus requiring novel interventions for its intensification.: Here are reviewed therapeutic vaccine candidates that are being developed to this goal. Among them, the Tat vaccine has been shown to promote immune restoration, including CD4+ T-cell recovery in low immunological responders, and to reduce the virus reservoirs well beyond what achieved with long-term suppressive cART.
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