High Level Activity of 2', 5'-Oligoadenylate Synthetase in Dog Serum

Iwata, Atsushi; Yamamoto, Akira; Fujino, Miyuki; Sato, Ichiro; Hosokawa-Kanai, Tomoko; Tuchiya, Kotaro; Ishihama, Akira; Sokawa, Yoshihiro

doi:10.1292/jvms.66.721

Cited by 3 publications

(2 citation statements)

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“…Previous studies demonstrated that the OAS-RNase L pathway is particularly important in murine macrophages and inhibits the replication of Picornaviridae including TMEV [93,97,98,99,100,101]. Interestingly, the OAS activity in canine serum is 10- to 100-fold higher than in cats, rabbits and guinea pigs, indicating a prominent role of OAS proteins in the canine humoral immune system [46]. However, the exact role of RNase L-dependent and independent functions of OAS proteins in the pathogenesis of CDV-induced leukoencephalitis remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, recent studies have shown that the virulence of CDV depends on the suppression of the IFN-I signaling pathway via interference with MDA5 and STAT2 signaling [45]. Interestingly, dogs exhibit a relatively high OAS serum activity compared to other animal species such as cats, rabbits and guinea pigs [46]. However, ISG expression has hardly been investigated in the CNS of CDV-infected dogs so far.…”

Section: Introductionmentioning

confidence: 99%

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Interferon-Stimulated Genes—Mediators of the Innate Immune Response during Canine Distemper Virus Infection

Klotz¹,

Gerhauser²

2019

IJMS

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The demyelinating canine distemper virus (CDV)-leukoencephalitis represents a translational animal model for multiple sclerosis. The present study investigated the expression of type I interferon (IFN-I) pathway members in CDV-induced cerebellar lesions to gain an insight into their role in lesion development. Gene expression of 110 manually selected genes in acute, subacute and chronic lesions was analyzed using pre-existing microarray data. Interferon regulatory factor (IRF) 3, IRF7, signal transducer and activator of transcription (STAT) 1, STAT2, MX protein, protein kinase R (PKR), 2′-5′-oligoadenylate synthetase (OAS) 1 and interferon-stimulated gene (ISG) 15 expression were also evaluated using immunohistochemistry. Cellular origin of STAT1, STAT2, MX and PKR were determined using immunofluorescence. CDV infection caused an increased expression of the antiviral effector proteins MX, PKR, OAS1 and ISG15, which probably contributed to a restricted viral replication, particularly in neurons and oligodendrocytes. This increase might be partly mediated by IRF-dependent pathways due to the lack of changes in IFN-I levels and absence of STAT2 in astrocytes. Nevertheless, activated microglia/macrophages showed a strong expression of STAT1, STAT2 and MX proteins in later stages of the disease, indicating a strong activation of the IFN-I signaling cascade, which might be involved in the aggravation of bystander demyelination.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Interferon-Stimulated Genes—Mediators of the Innate Immune Response during Canine Distemper Virus Infection

Klotz¹,

Gerhauser²

2019

IJMS

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The Mammalian 2′-5′ Oligoadenylate Synthetase Gene Family: Evidence for Concerted Evolution of Paralogous Oas1 Genes in Rodentia and Artiodactyla

et al. 2006

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Multiple 2'-5' oligoadenylate (2-5A) synthetases are important components of innate immunity in mammals. Gene families encoding these proteins have previously been studied mainly in humans and mice. To reconstruct the evolution of this gene family in mammals, a search for additional 2-5A synthetase genes was performed in rat, cattle, pig, and dog. Twelve 2'-5' oligoadenylate synthetase (Oas) genes were identified in the rat genome, including eight Oas1 genes, two Oas1 pseudogenes, single copies of Oas2 and Oas3, and two Oas-like genes, Oasl1 and Oasl2. Four OAS genes were detected in the pig genome and five OAS genes were found in both the cattle and dog genomes. An OAS3 gene was not found in either the cattle or the pig genome. While two tandemly duplicated OAS-like (OASL) genes were identified in the dog genome, only a single OASL orthologue was found in both the cattle and the pig genomes. The bovine and porcine OASL genes contain premature stop codons and encode truncated proteins, which lack the typical C-terminal double ubiquitin domains. The cDNA sequences of the rat, cattle, pig, and dog OAS genes were amplified, sequenced and compared with each other and with those in the human, mouse, horse, and chicken genomes. Evidence of concerted evolution of paralogous 2'-5' oligoadenylate synthetase 1 genes was obtained in rodents (Rodentia) and even-toed ungulates (Artiodactyla). Calculations using the nonparametric Kolmogorov-Smirnov test suggested that the homogenization of paralogous OAS1 sequences was due to gene conversion rather than stabilizing selection.

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