Zheng Chunfu, Su Chenhe
Institutes of Biology and Medical Sciences, Soochow University, Suzhou, 215123, China.
Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, AB, T2N 4N1, Canada.
Virol J. 2017 Feb 21;14(1):35. doi: 10.1186/s12985-017-0709-5.
Herpes simplex virus 1 (HSV-1) is an archetypal member of the alphaherpesvirus subfamily with a large genome encoding over 80 proteins, many of which play a critical role in virus-host interactions and immune modulation. Upon viral infections, the host cells activate innate immune responses to restrict their replications. Peroxisomes, which have long been defined to regulate metabolic activities, are reported to be important signaling platforms for antiviral innate immunity. It has been verified that signaling from peroxisomal MAVS (MAVS-Pex) triggers a rapid interferon (IFN) independent IFN-stimulated genes (ISGs) production against invading pathogens. However, little is known about the interaction between DNA viruses such as HSV-1 and the MAVS-Pex mediated signaling.
HSV-1 could activate the MAVS-Pex signaling pathway at a low multiplicity of infection (MOI), while infection at a high MOI dampens MAVS-Pex induced immediately early ISGs production. A high-throughput screen assay reveals that HSV-1 tegument protein VP16 inhibits the immediate early ISGs expression downstream of MAVS-Pex signaling. Moreover, the expression of ISGs was recovered when VP16 was knockdown with its specific short hairpin RNA.
HSV-1 blocks MAVS-Pex mediated early ISGs production through VP16 to dampen the immediate early antiviral innate immunity signaling from peroxisomes.
单纯疱疹病毒1型（HSV-1）是α疱疹病毒亚科的典型成员，其基因组庞大，编码超过80种蛋白质，其中许多在病毒与宿主的相互作用及免疫调节中发挥关键作用。病毒感染后，宿主细胞会激活先天免疫反应以限制其复制。过氧化物酶体长期以来被定义为调节代谢活动的细胞器，据报道它是抗病毒先天免疫的重要信号平台。已经证实，过氧化物酶体中的线粒体抗病毒信号蛋白（MAVS-Pex）发出的信号会触发针对入侵病原体的快速干扰素（IFN）非依赖性干扰素刺激基因（ISGs）的产生。然而，对于诸如HSV-1等DNA病毒与MAVS-Pex介导的信号之间的相互作用知之甚少。
HSV-1在低感染复数（MOI）时可激活MAVS-Pex信号通路，而高MOI感染会抑制MAVS-Pex诱导的立即早期ISGs的产生。高通量筛选试验表明，HSV-1被膜蛋白VP16抑制MAVS-Pex信号下游的立即早期ISGs表达。此外，当用其特异性短发夹RNA敲低VP16时，ISGs的表达得以恢复。
HSV-1通过VP16阻断MAVS-Pex介导的早期ISGs产生，以减弱过氧化物酶体的立即早期抗病毒先天免疫信号。
