HIV regulation of amyloid beta production.
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 (Abeta) increases during normal aging but Abeta accumulation appears to accelerate in HIV infection. HIV Tat protein inhibits the major Abeta-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 beta chemokine, CCL2/MCP-1, associated with HIV migration to the brain, also causes an increase in Abeta. These findings may explain the continued cognitive dysfunction found in HIV-infected individuals controlled on antiviral therapy.
Pulliam
Lynn
L
Veterans Affair Medical Center, San Francisco, University of California, San Francisco, CA 94121, USA. Lynn.Pulliam@ucsf.edu
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D018932:Chemokine CCL2 / Q000378:metabolism*; D015658:HIV Infections / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D006801:Humans; D011993:Recombinant Fusion Proteins / Q000378:metabolism*; D000077022:Survivin; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D051017:Apoptosis Regulatory Proteins; D018932:Chemokine CCL2; C512124:HIV-TAT-survivin (T34A) protein; D011993:Recombinant Fusion Proteins; D000077022:Survivin; D054322:tat Gene Products, Human Immunodeficiency Virus