Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, United States.
Cell Signal. 2012 Jul;24(7):1414-9. doi: 10.1016/j.cellsig.2012.02.016. Epub 2012 Mar 2.
Autophagy plays important roles during innate and adaptive immune responses to pathogens, including virus infection. Viruses develop ways to subvert the pathway for their own benefit in order to escape restriction by autophagy, leading to increased viral replication and/or control over apoptosis of their host cells. The effects of HIV infection on the autophagic pathway in host cells have been little documented. Using the susceptible Jurkat cell line and CD4(+) T cells, we studied the relationship of HIV-1 and -2 infections with autophagy. We found that HIV infections significantly increase transcription of ULK1, a member of the autophagy-initiated complex. Two ubiquitin-like conjugation systems, the Atg12 conjugation system and the microtubule-associated protein L chain 3 (LC3) conjugation system that control the elongation of the autophore to form the autophagosome, were activated after HIV infection, with upregulation of Atg12-Atg5 complex and increased transcription of LC3, and formed more autophagosome in infected cells detected using an EM assay. We also found that HIV-1 induced more autophagic death in Jurkat cells relative to HIV-2, and the inhibition of autophagy with 3MA and Beclin-1 knockdown decreased HIV-1 replication significantly. The results indicate that HIV is able to induce the autophagic signaling pathway in HIV-infected host cells, which may be required for HIV infection-mediated apoptotic cell death.
自噬在病原体（包括病毒感染）固有和适应性免疫反应中发挥重要作用。病毒会发展出有利于自身的方式来颠覆该途径，从而逃避自噬的限制，导致病毒复制增加和/或控制宿主细胞的细胞凋亡。HIV 感染对宿主细胞自噬途径的影响鲜有记录。我们使用易感性 Jurkat 细胞系和 CD4(+) T 细胞研究了 HIV-1 和 -2 感染与自噬的关系。我们发现 HIV 感染可显著增加自噬起始复合物成员 ULK1 的转录。两种泛素样连接系统，即 Atg12 连接系统和微管相关蛋白 L 链 3 (LC3) 连接系统，控制自噬体的伸长以形成自噬体，在 HIV 感染后被激活，Atg12-Atg5 复合物上调，LC3 的转录增加，并用 EM 检测到感染细胞中形成了更多的自噬体。我们还发现 HIV-1 诱导 Jurkat 细胞的自噬性死亡比 HIV-2 更多，并且用 3MA 和 Beclin-1 敲低抑制自噬会显著降低 HIV-1 复制。结果表明，HIV 能够诱导感染宿主细胞的自噬信号通路，这可能是 HIV 感染介导的凋亡性细胞死亡所必需的。
