title: Activation of type I interferon signaling in the parotid and exorbital lachrymal glands during the acute phase of encephalomyocarditis (EMC) virus infection in mice.
abstract: The present study was carried out to clarify the mechanisms of EMC virus-induced sialodacryoadenitis in mice during the acute phase infection focusing on the activation of type I interferon (IFN) signaling in the parotid and exorbital lachrymal glands. In the parotid gland, a few apoptotic acinar cells were detected at 2days post inoculation (DPI). The ratio of apoptotic acinar cells increased at 3 and 4DPI. On the other hand, in the exorbital lachrymal gland, apoptosis of acinar cells and infiltration of inflammatory cells mainly composed of mononuclear cells started at 3DPI, and prominent acinar cell damage developed at 4DPI. Viral RNA was detected at 3 and 4DPI in both glands and the expression level was higher in the exorbital lachrymal gland than in the parotid gland. The up-regulation of IFN-stimulated genes (ISGs), such as Irf7, Pkr and Oas, was quickly induced at 2DPI in the parotid gland, and this probably contributed to suppress viral replication and to eliminate affected cells by apoptosis. In the exorbital lachrymal gland, the expression levels of ISGs mRNAs were not elevated at 2DPI, suggesting no induction of an effective anti-viral response such as apoptosis at this time point. In the exorbital lachrymal gland, the mRNA expression of IFN beta and IFN alpha (type I IFNs) was weak- to strong-positive at 1DPI, and became negative at 2DPI. The weak- to strong-positive expression of IFNs at 1DPI is likely related to the abrupt viral replication and pathological changes in the exorbital lachrymal gland through activating the negative feedback regulation that depressed the IFN signaling cascade at 2DPI. In conclusion, the present study showed the changes in factors involved in the activation of type I IFN signaling cascade in the parotid and exorbital lachrymal glands and their differences between the two glands during the acute phase of EMC virus infection in mice.
authors.affiliation: Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Japan. Electronic address: aohguchi-yamauchi@umin.ac.jp.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Ohguchi
authors.affiliation: Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yamauchi
authors.affiliation: Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Japan.
authors.forename: Kunio
authors.initials: K
authors.lastname: Doi
authors.affiliation: Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakayama
mesh_terms: D000208:Acute Disease; D000818:Animals; D018188:Cardiovirus Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D004686:Encephalomyocarditis virus / Q000235:genetics / Q000502:physiology; D015870:Gene Expression; D054884:Host-Pathogen Interactions; D050839:Interferon Regulatory Factor-7 / Q000235:genetics; D007370:Interferon Type I / Q000235:genetics*; D016898:Interferon-alpha / Q000235:genetics; D007765:Lacrimal Apparatus / Q000378:metabolism* / Q000821:virology; D008297:Male; D008811:Mice, Inbred DBA; D010306:Parotid Gland / Q000378:metabolism* / Q000821:virology; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*; D013997:Time Factors
chemical_list: D050839:Interferon Regulatory Factor-7; D007370:Interferon Type I; D016898:Interferon-alpha; C494235:Irf7 protein, mouse; D012367:RNA, Viral
keywords: Encephalomyocarditis virus; Exorbital lachrymal gland; Mice; Parotid gland; Type I interferon