Iran J Vet Res. 2021;22(3):209-216. doi: 10.22099/ijvr.2021.38240.5568.
The dUTPase of caprine arthritis-encephalitis virus negatively regulates interferon signaling pathway.
Iranian journal of veterinary research
J Shi, X Li, M Zhu, H Chi, Y Song, J Wang, J Huang
Affiliations
Affiliations
- MSc Student in Biology, Department of Microbiology & Immunology, School of Life Sciences, Tianjin University, Tianjin, 300072, China.
- These authors contributed equally to this work.
- Departmet of Microbiology & Immunology, School of Life Sciences, Tianjin University, Tianjin, 300072, China.
PMID: 34777521
PMCID: PMC8573393 DOI: 10.22099/ijvr.2021.38240.5568
Abstract
BACKGROUND: Deoxyuracil triphosphate nucleotide (dUTP) pyrophosphatase (dUTPase, DU) is an enzyme of caprine arthritis-encephalitis virus (CAEV) that minimizes incorporation of dUTP into the DNA. Caprine arthritis-encephalitis virus relies partly on its ability to escape from innate immunity to cause persistent infections. Interferon β (IFN-β) is an important marker for evaluating the innate immune system, and it has a broad spectrum of antiviral activity.
AIMS: This study was conducted to investigate the details of the IFN-β response to CAEV infection.
METHODS: The expression of IFN-β and the proliferation of Sendai virus (SeV) and vesicular stomatitis virus (VSV) were determined by real-time quantitative polymerase chain reaction (qPCR). The effect of DU on the IFN signaling pathway was evaluated using luciferase reporter assays.
RESULTS: In our study, the expression of IFN-β was significantly inhibited and the proliferation of SeV and VSV was promoted in cells overexpressing CAEV-DU. DU affected interferon stimulated response element (ISRE) and IFN-β promoter activities induced by RIG-I/MDA5/MAVS/TBK1 pathway, while did not affect them induced by interferon regulatory factor 3 (IRF3-5D).
CONCLUSION: DU protein downregulated the production of IFN-β by inhibiting the activity of the signal transduction molecules upstream of IRF3, thereby, helping CAEV escape innate immunity. Findings of this work provide an evidence to understand the persistent infection and multiple system inflammation of CAEV.
Keywords: Caprine arthritis-encephalitis virus; Innate immunity; Interferon type I; dUTPase
Conflict of interest statement
The authors declare no financial and/or non-financial competing interests.
References
- J Virol. 1992 Mar;66(3):1791-4 - PubMed
- Biochem J. 2017 Mar 15;474(7):1163-1174 - PubMed
- Aust Vet J. 1995 Sep;72(9):341-5 - PubMed
- Curr Protein Pept Sci. 2001 Dec;2(4):381-8 - PubMed
- PLoS Pathog. 2017 Jun 7;13(6):e1006347 - PubMed
- Vaccines (Basel). 2020 Apr 29;8(2): - PubMed
- J Virol. 2009 Jan;83(2):1152-5 - PubMed
- J Bacteriol. 1988 Mar;170(3):1069-75 - PubMed
- Arch Virol. 2020 Jul;165(7):1557-1567 - PubMed
- PLoS Pathog. 2011 Oct;7(10):e1002292 - PubMed
- Immunity. 2011 May 27;34(5):680-92 - PubMed
- Vet J. 2009 Jun;180(3):399-401 - PubMed
- Prev Vet Med. 2018 Mar 1;151:13-20 - PubMed
- Trop Anim Health Prod. 2012 Jan;44(1):1-3 - PubMed
- Acc Chem Res. 2009 Jan 20;42(1):97-106 - PubMed
- Infect Immun. 1983 Jul;41(1):67-73 - PubMed
- J Virol. 1986 Nov;60(2):385-93 - PubMed
- Virol J. 2014 Feb 07;11:22 - PubMed
- J Vet Med Sci. 2012 Dec;74(12):1657-9 - PubMed
- J Virol. 1997 Jun;71(6):4522-30 - PubMed
- J Virol. 1989 Jun;63(6):2578-84 - PubMed
- J Exp Med. 2008 Jul 7;205(7):1601-10 - PubMed
- Viruses. 2013 Aug 15;5(8):2005-18 - PubMed
- Prev Vet Med. 2020 Mar;176:104886 - PubMed
- Arch Virol. 2012 Aug;157(8):1463-9 - PubMed
- J Virol. 2010 Sep;84(18):9240-53 - PubMed
- J Gen Virol. 1982 Apr;59(Pt 2):345-56 - PubMed
- J Virol. 2017 Oct 13;91(21): - PubMed
- Retrovirology. 2015 Aug 12;12:70 - PubMed
- Arch Virol. 1981;67(1):111-7 - PubMed
- Vet Res Commun. 2010 Jun;34 Suppl 1:S47-51 - PubMed
- Science. 2015 Mar 13;347(6227):aaa2630 - PubMed
- Nucleic Acids Res. 1990 Jul 25;18(14):4105-10 - PubMed
- Vet Res. 2012 May 16;43:43 - PubMed
- Virology. 1990 Nov;179(1):347-64 - PubMed
- J Vet Diagn Invest. 2020 Jul;32(4):589-593 - PubMed
- J Virol. 2014 Jul;88(14):7776-85 - PubMed
- Vaccine. 2017 Jan 11;35(3):481-488 - PubMed
- Arch Virol. 2013 Oct;158(10):2135-41 - PubMed
- Comp Immunol Microbiol Infect Dis. 2013 Jul;36(4):397-404 - PubMed
- Comp Immunol Microbiol Infect Dis. 2012 May;35(3):259-69 - PubMed
- J Gen Virol. 2002 Oct;83(Pt 10):2339-2345 - PubMed
- Annu Rev Virol. 2015 Nov;2(1):549-72 - PubMed
- Vet J. 2010 Mar;183(3):328-31 - PubMed
- J Immunol. 2019 May 15;202(10):2957-2970 - PubMed
- Front Immunol. 2018 Dec 18;9:3023 - PubMed
- Viruses. 2018 Aug 17;10(8): - PubMed
- J Vis Exp. 2011 Oct 09;(56): - PubMed
- J Dairy Sci. 2012 Apr;95(4):1617-22 - PubMed
- EMBO J. 1993 Nov;12(11):4425-31 - PubMed
- Hum Vaccin Immunother. 2014;10(11):3270-85 - PubMed
- Proc Natl Acad Sci U S A. 2013 Feb 5;110(6):E448-57 - PubMed
- Vet Immunol Immunopathol. 2017 Sep;191:80-93 - PubMed
- Vet Res. 2004 May-Jun;35(3):257-74 - PubMed
- Acta Biochim Pol. 1997;44(2):159-71 - PubMed
- J Virol Methods. 2017 May;243:98-104 - PubMed
- Curr Protoc Chem Biol. 2017 Sep 14;9(3):147-157 - PubMed
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