Investigating HIV-1 TAT protein role in Atherogenesis

• Published in: The Journal of immunology (1950) 2023-05, Vol.210 (Supplement_1), p.153-153.18
• Main Authors: Kirk, Cassandra Lee, Moriarty, Alina, Stahr, Natalie Ann, Keeter, W Coles, Ma, Shelby, Kim, Woong-Ki, Guo, Ming-Lei, Galkina, Elena
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.210.Supp.153.18

With the recent development of antiretroviral therapy, HIV patients can live a long and normal lifespan. Recent evidence demonstrates an increased incidence of developing cardiovascular diseases (CVD) specifically atherosclerosis in aged HIV-infected patients. The adaptive and innate immune responses play a complex specific role in atherosclerotic plaque burden. However, specific mechanisms of the implication of the immune system in HIV-accelerated atherosclerosis are unclear. The protein Trans-Activator of Transcription–TAT is strongly associated with HIV infection as it enhances the efficiency of viral transcription. To understand the contributions of TAT protein in HIV-associated atherogenesis, a doxycycline-inducible astrocyte-specific HIV-1 TAT transgenic mouse was used. An injection of recombinant adeno-associated virus vector (AAV) encoding a gain-of-function mutant PCSK9 into mice and feeding with high fat with added cholesterol (DDC) and doxycycline (Dox) was used to promote atherosclerosis and TAT expression. After 16 wks of feeding, various tissues were collected and used for flow cytometry analysis (FACS) for immune profiling. Our preliminary data suggest that TAT is involved in the regulation of peripheral blood neutrophil numbers and therefore can serve as a regulator of inflammation in HIV-associated atherosclerosis. Future analysis will provide insight into potential mechanisms of HIV TAT-dependent involvement in atherosclerosis development and progression. This work was supported by project –initiation funds from the Center for Integrative Neuroscience and Inflammatory Diseases at EVMS and NIH NHLBI R01HL142129-04S1 grant.