丙型肝炎病毒核心蛋白通过 TLR2、JNK 和 MEK1/2 依赖性上调 TNF-α 和 IL-6 增强人巨噬细胞中的 HIV-1 复制。
Hepatitis C virus core protein enhances HIV-1 replication in human macrophages through TLR2, JNK, and MEK1/2-dependent upregulation of TNF-α and IL-6.
机构信息
Microbiology and Immunology Graduate Program, Drexel University College of Medicine, Philadelphia, PA 19102, USA; Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19102, USA.
Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19102, USA; Master of Science in Forensic Science Program, Professional Studies in the Health Sciences, Drexel University College of Medicine, Philadelphia, PA 19102, USA.
出版信息
FEBS Lett. 2014 Sep 17;588(18):3501-10. doi: 10.1016/j.febslet.2014.08.009. Epub 2014 Aug 14.
Despite their differential cell tropisms, HIV-1 and HCV dramatically influence disease progression in coinfected patients. Macrophages are important target cells of HIV-1. We hypothesized that secreted HCV core protein might modulate HIV-1 replication. We demonstrate that HCV core significantly enhances HIV-1 replication in human macrophages by upregulating TNF-α and IL-6 via TLR2-, JNK-, and MEK1/2-dependent pathways. Furthermore, we show that TNF-α and IL-6 secreted from HCV core-treated macrophages reactivates monocytic U1 cells latently infected with HIV-1. Our studies reveal a previously unrecognized role of HCV core by enhancing HIV-1 infection in macrophages.
尽管 HIV-1 和 HCV 具有不同的细胞嗜性，但它们都会显著影响合并感染患者的疾病进展。巨噬细胞是 HIV-1 的重要靶细胞。我们假设分泌的 HCV 核心蛋白可能会调节 HIV-1 的复制。我们证明 HCV 核心通过 TLR2、JNK 和 MEK1/2 依赖性途径上调 TNF-α 和 IL-6，从而显著增强人巨噬细胞中的 HIV-1 复制。此外，我们还表明，从 HCV 核心处理的巨噬细胞中分泌的 TNF-α 和 IL-6 可重新激活潜伏感染 HIV-1 的单核细胞 U1 细胞。我们的研究揭示了 HCV 核心通过增强巨噬细胞中的 HIV-1 感染而发挥的以前未被认识的作用。
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