Long-term HIV-1 Tat Expression in the Brain Led to Neurobehavioral, Pathological, and Epigenetic Changes Reminiscent of Accelerated Aging

Date

2020-02-01

Authors

Zhao, Xiaojie
Fan, Yan
Vann, Philip H.
Wong, Jessica M.
Sumien, Nathalie
He, Johnny J.

ORCID

0000-0002-0077-9873 (Sumien, Nathalie)

Journal Title

Journal ISSN

Volume Title

Publisher

International Society on Aging and Disease

Abstract

HIV infects the central nervous system and causes HIV/neuroAIDS, which is predominantly manifested in the form of mild cognitive and motor disorder in the era of combination antiretroviral therapy. HIV Tat protein is known to be a major pathogenic factor for HIV/neuroAIDS through a myriad of direct and indirect mechanisms. However, most, if not all of studies involve short-time exposure of recombinant Tat protein in vitro or short-term Tat expression in vivo. In this study, we took advantage of the doxycycline-inducible brain-specific HIV-1 Tat transgenic mouse model, fed the animals for 12 months, and assessed behavioral, pathological, and epigenetic changes in these mice. Long-term Tat expression led to poorer short-and long-term memory, lower locomotor activity and impaired coordination and balance ability, increased astrocyte activation and compromised neuronal integrity, and decreased global genomic DNA methylation. There were sex- and brain region-dependent differences in behaviors, pathologies, and epigenetic changes resulting from long-term Tat expression. All these changes are reminiscent of accelerated aging, raising the possibility that HIV Tat contributes, at least in part, to HIV infection-associated accelerated aging in HIV-infected individuals. These findings also suggest another utility of this model for HIV infection-associated accelerated aging studies.

Description

Citation

Zhao, X., Fan, Y., Vann, P. H., Wong, J. M., Sumien, N., & He, J. J. (2020). Long-term HIV-1 Tat Expression in the Brain Led to Neurobehavioral, Pathological, and Epigenetic Changes Reminiscent of Accelerated Aging. Aging and disease, 11(1), 93-107. https://doi.org/10.14336/AD.2019.0323

Rights

Copyright : © 2019 Zhao et al.

License

Attribution 4.0 International (CC BY 4.0)