title: M1 of Murine Gamma-Herpesvirus 68 Induces Endoplasmic Reticulum Chaperone Production.
abstract: Viruses rely on host chaperone network to support their infection. In particular, the endoplasmic reticulum (ER) resident chaperones play key roles in synthesizing and processing viral proteins. Influx of a large amount of foreign proteins exhausts the folding capacity in ER and triggers the unfolded protein response (UPR). A fully-executed UPR comprises signaling pathways that induce ER folding chaperones, increase protein degradation, block new protein synthesis and may eventually activate apoptosis, presenting both opportunities and threats to the virus. Here, we define a role of the MHV-68M1 gene in differential modulation of UPR pathways to enhance ER chaperone production. Ectopic expression of M1 markedly induces ER chaperone genes and expansion of ER. The M1 protein accumulates in ER during infection and this localization is indispensable for its function, suggesting M1 acts from the ER. We found that M1 protein selectively induces the chaperon-producing pathways (IRE1, ATF6) while, interestingly, sparing the translation-blocking arm (PERK). We identified, for the first time, a viral factor capable of selectively intervening the initiation of ER stress signaling to induce chaperon production. This finding provides a unique opportunity of using viral protein as a tool to define the activation mechanisms of individual UPR pathways.
authors.affiliation: Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California 90095.|Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: Jiaying
authors.initials: J
authors.lastname: Feng
authors.affiliation: Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California 90095.
authors.forename: Danyang
authors.initials: D
authors.lastname: Gong
authors.affiliation: Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California 90095.|Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Fu
authors.affiliation: Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California 90095.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Wu
authors.affiliation: Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California 90095.
authors.forename: Jane
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California 90095.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Chang
authors.affiliation: Zhejiang University, Hangzhou, People's Republic of China.|Department of Anesthesiology, University of California, Los Angeles, California 90095.
authors.forename: Jingting
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology, University of California, Los Angeles, California 90095.
authors.forename: Gang
authors.initials: G
authors.lastname: Lu
authors.affiliation: Department of Anesthesiology, University of California, Los Angeles, California 90095.
authors.forename: Yibin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California 90095.|Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: Ren
authors.initials: R
authors.lastname: Sun
mesh_terms: D051702:Activating Transcription Factor 6 / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000821:virology; D015870:Gene Expression; D006566:Herpesviridae Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018832:Molecular Chaperones / Q000096:biosynthesis* / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D018144:Rhadinovirus / Q000502:physiology*; D015398:Signal Transduction; D056811:Unfolded Protein Response
chemical_list: D051702:Activating Transcription Factor 6; D008565:Membrane Proteins; D018832:Molecular Chaperones; C486556:Ern2 protein, mouse; D017346:Protein Serine-Threonine Kinases