Pulliam Lynn
Veterans Affair Medical Center, San Francisco, University of California, San Francisco, CA 94121, USA.
J Neuroimmune Pharmacol. 2009 Jun;4(2):213-7. doi: 10.1007/s11481-009-9151-9. Epub 2009 Mar 14.
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.
抗逆转录病毒疗法用于治疗HIV感染，延长了HIV感染者的生存期。然而，慢性HIV感染和衰老的影响正引发HIV并发症的另一个方面。HIV治疗可使免疫系统平静下来，并将病毒复制降低到检测不到的水平，但病毒仍然存在。在大脑中，淀粉样β蛋白（Aβ）在正常衰老过程中会增加，但在HIV感染中Aβ的积累似乎会加速。HIV反式激活蛋白（Tat）抑制主要的Aβ降解酶中性内肽酶，Tat富含半胱氨酸的结构域对于这种抑制作用至关重要。在这篇小型综述中，我们还纳入了新数据，即与HIV向大脑迁移相关的β趋化因子CCL2/单核细胞趋化蛋白-1（MCP-1）也会导致Aβ增加。这些发现可能解释了在接受抗病毒治疗得到控制的HIV感染者中持续存在的认知功能障碍。
