title: Herpes simplex virus 1 infection dampens the immediate early antiviral innate immunity signaling from peroxisomes by tegument protein VP16.
abstract: 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.
authors.affiliation: Institutes of Biology and Medical Sciences, Soochow University, Suzhou, 215123, China. zheng.alan@hotmail.com.|Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, AB, T2N 4N1, Canada. zheng.alan@hotmail.com.
authors.forename: Chunfu
authors.initials: C
authors.lastname: Zheng
authors.affiliation: Institutes of Biology and Medical Sciences, Soochow University, Suzhou, 215123, China.
authors.forename: Chenhe
authors.initials: C
authors.lastname: Su
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D002460:Cell Line; D017405:Herpes Simplex Virus Protein Vmw65 / Q000378:metabolism*; D018259:Herpesvirus 1, Human / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D006801:Humans; D057131:Immune Evasion; D007113:Immunity, Innate; D053402:PHEX Phosphate Regulating Neutral Endopeptidase / Q000378:metabolism; D020675:Peroxisomes / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D017405:Herpes Simplex Virus Protein Vmw65; C505371:MAVS protein, human; D053402:PHEX Phosphate Regulating Neutral Endopeptidase; C506231:PHEX protein, human
keywords: HSV-1; Immune evasion; MAVS-Pex; VP16