Abstract
The use of antiretroviral therapy for HIV infection has extended the survival of individuals living with HIV. However, the effects of chronic HIV infection and aging are introducing another facet of HIV complications. HIV therapy can calm the immune system and lower viral replication to undetectable but the virus is still present. In the brain, amyloid beta (Aβ) increases during normal aging but Aβ accumulation appears to accelerate in HIV infection. HIV Tat protein inhibits the major Aβ-degrading enzyme neprilysin with the cysteine-rich domain of Tat being essential for this inhibition. In this minireview, we also include new data that the β chemokine, CCL2/MCP-1, associated with HIV migration to the brain, also causes an increase in Aβ. These findings may explain the continued cognitive dysfunction found in HIV-infected individuals controlled on antiviral therapy.
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Acknowledgement
The author thanks the Advanced Bioscience Resource for the brain tissue and the National Institutes of Health for their support (LP-RO1MH068213). The author thanks Dr. Hans Rempel, Dr. Bing Sun, Cyrus Calosing and Laure Blouin for technical expertise and editorial comments.