Thaney Victoria E, Kaul Marcus
1 Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute , La Jolla, California.
2 Division of Biomedical Sciences, School of Medicine, University of California , Riverside, Riverside, California.
Viral Immunol. 2019 Jan/Feb;32(1):7-14. doi: 10.1089/vim.2018.0085. Epub 2018 Sep 27.
Infection with Human Immunodeficiency Virus (HIV)-1 continues to cause HIV-associated neurocognitive disorders despite combined antiretroviral therapy. Interferons (IFNs) are important for any antiviral immune response, but the lasting production of IFNα causes exhaustive activation leading eventually to progression to AIDS. Expression of IFNα in the HIV-exposed central nervous system has been linked to cognitive impairment and inflammatory neuropathology. In contrast, IFNβ exerts anti-inflammatory effects, appears to control, at least temporarily, lentiviral infection in the brain and provides neuroprotection. The dichotomy of type I IFN effects on HIV-1 infection and the associated brain injury will be discussed in this review, because the underlying mechanisms require further investigation to allow harnessing these innate immune factors for therapeutic purposes.
尽管采用了联合抗逆转录病毒疗法,但人类免疫缺陷病毒1型(HIV-1)感染仍会导致与HIV相关的神经认知障碍。干扰素(IFN)对任何抗病毒免疫反应都很重要,但IFNα的持续产生会导致过度激活,最终导致发展为艾滋病。在暴露于HIV的中枢神经系统中,IFNα的表达与认知障碍和炎症性神经病理学有关。相比之下,IFNβ具有抗炎作用,似乎至少在短期内能控制大脑中的慢病毒感染,并提供神经保护。本综述将讨论I型干扰素对HIV-1感染及相关脑损伤影响的二分法,因为其潜在机制需要进一步研究,以便将这些先天免疫因子用于治疗目的。