γ干扰素通过上调I型干扰素表达协同抑制猪传染性胃肠炎病毒的复制
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摘要
为探索干扰素(IFN)在猪消化道冠状病毒的预防和治疗中的作用,通过反转录定量PCR(reverse transcription-q PCR,RT-qPCR)和间接免疫荧光试验,分别检测猪传染性胃肠炎病毒(TGEV)拷贝数和TGEV核衣壳蛋白的表达,发现猪源IFN-γ能够显著抑制TGEV在猪睾丸细胞中的复制,并且相同质量浓度的IFN-γ比IFN-α能更有效地抑制TGEV的复制,与猪源IFN-α有明显的协同抑制作用。对其机制进一步探索,发现IFN-γ能够不依赖于I型干扰素发挥直接抗病毒活性,但是能够通过诱导I型干扰素表达水平的上调,增加其抗病毒活性。结果表明,IFN-γ通过诱导I型干扰素的表达与I型干扰素协同抑制TGEV的复制,对预防和治疗TGEV感染有重要意义。
The purpose of this study was to explore the preventive and therapeutic effects of interferon(IFN) in swine enteric coronavirus.Transmissible gastroenteritis virus(TGEV) copy number and TGEV nucleocapsid protein expression were detected by reverse transcription-q PCR(RT-q PCR) and indirect immunofluorescence assay,respectively.The results showed that porcine IFN-γ can significantly inhibit TGEV infection in ST cells, and IFN-γ exhibited more effective to suppress TGEV infection than IFN-α at the same mass concentration.What's more,IFN-γ and IFN-α had obvious synergistic inhibition of TGEV.We further explored the mechanism and found that IFN-γ can exert antiviral activity independent of type Ⅰinterferon,but IFN-γ can increase its antiviral activity by inducing up-regulation of typeⅠinterferon expression level,which suggested that IFN-γ may play a synergistic role in anti-TGEV replication by inducing typeⅠIFN expression.It is important to the prevention and treatment of TGEV infection.
The purpose of this study was to explore the preventive and therapeutic effects of interferon(IFN) in swine enteric coronavirus.Transmissible gastroenteritis virus(TGEV) copy number and TGEV nucleocapsid protein expression were detected by reverse transcription-q PCR(RT-q PCR) and indirect immunofluorescence assay,respectively.The results showed that porcine IFN-γ can significantly inhibit TGEV infection in ST cells, and IFN-γ exhibited more effective to suppress TGEV infection than IFN-α at the same mass concentration.What's more,IFN-γ and IFN-α had obvious synergistic inhibition of TGEV.We further explored the mechanism and found that IFN-γ can exert antiviral activity independent of type Ⅰinterferon,but IFN-γ can increase its antiviral activity by inducing up-regulation of typeⅠinterferon expression level,which suggested that IFN-γ may play a synergistic role in anti-TGEV replication by inducing typeⅠIFN expression.It is important to the prevention and treatment of TGEV infection.
引文
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[12]GUO L,LUO X,LI R,et al.Porcine epidemic diarrhea virus infection inhibits interferon signaling by targeted degradation of STAT1[J].Journal of Virology,2016,90(18):8281-8292.
[13]SPLICHAL I,REHAKOVA Z,SINKORA M,et al.In vivo study of interferon-alpha-secreting cells in pig foetal lymphohaematopoietic organs following in utero TGEV coronavirus injection[J].Research in Immunology,1997,148(4):247-256.
[14]BARKHOUSE D A,GARCIA S A,BONGIORNO E K,et al.Expression of interferon gamma by a recombinant rabies virus strongly attenuates the pathogenicity of the virus via induction of typeⅠinterferon[J].Journal of Virology,2015,89(1):312-322.
[15]SAINZ B Jr.,MOSSEL E C,PETERS C J,et al.Interferon-beta and interferon-gamma synergistically inhibit the replication of severe acute respiratory syndrome-associated coronavirus(SARS-CoV)[J].Virology,2004,329(1):11-17.
[16]OKUSE C,RINAUDO J A,FARRAR K,et al.Enhancement of antiviral activity against hepatitis C virus in vitro by interferon combination therapy[J].Antiviral Research,2005,65(1):23-34.
[17]SCHRODER K,HERTZOG P J,RAVASI T,et al.Interferon-γ:an overview of signals,mechanisms and functions[J].Journal of Leukocyte Biology,2004,75(2):163-189.
[18]SOZZANI S,DEL PRETE A,BOSISIO D.Dendritic cell recruitment and activation in autoimmunity[J].Journal of Autoimmunity,2017,85:126-140.
[2]PESTKA S.The interferons:50 years after their discovery,there is much more to learn[J].Journal of Biological Chemistry,2007,282(28):20047-20051.
[3]POLLARD K M,CAUVI D M,TOOMEY C B,et al.Interferon-gamma and systemic autoimmunity[J].Discovery Medicine,2013,16(87):123-131.
[4]VAN BOXEL-DEZAIRE A H,STARK G R.Cell type-specific signaling in response to interferon-γ[J].Current Topics in Microbiology and Immunology,2007,316:119-154.
[5]LIN C M,GAO X,OKA T,et al.Antigenic relationships among porcine epidemic diarrhea virus and transmissible gastroenteritis virus strains[J].Journal of Virology,2015,89(6):3332-3342.
[6]XIA L,YANG Y,WANG J,et al.Impact of TGEV infection on the pig small intestine[J].Virology Journal,2018,15(1):102.
[7]GERDTS V,ZAKHARTCHOUK A.Vaccines for porcine epidemic diarrhea virus and other swine coronaviruses[J].Veterinary Microbiology,2017,206:45-51.
[8]ZHANG Q,YOO D.Immune evasion of porcine enteric coronaviruses and viral modulation of antiviral innate signaling[J].Virus Research,2016,226:128-141.
[9]BIGLEY N J.Complexity of interferon-gamma interactions with HSV-1[J].Frontier in Immunology,2014,5:15.
[10]ZHU L,YANG X,MOU C,et al.Transmissible gastroenteritis virus does not suppress IFN-βinduction but is sensitive to IFN in IPEC-J2 cells[J].Veterinary Microbiology,2017,199:128-134.
[11]RIFFAULT S,CARRAT C,VAN REETH K,et al.Interferon-alpha-producing cells are localized in gutassociated lymphoid tissues in transmissible gastroenteritis virus(TGEV)infected piglets[J].Veterinary Research,2001,32(1):71-79.
[12]GUO L,LUO X,LI R,et al.Porcine epidemic diarrhea virus infection inhibits interferon signaling by targeted degradation of STAT1[J].Journal of Virology,2016,90(18):8281-8292.
[13]SPLICHAL I,REHAKOVA Z,SINKORA M,et al.In vivo study of interferon-alpha-secreting cells in pig foetal lymphohaematopoietic organs following in utero TGEV coronavirus injection[J].Research in Immunology,1997,148(4):247-256.
[14]BARKHOUSE D A,GARCIA S A,BONGIORNO E K,et al.Expression of interferon gamma by a recombinant rabies virus strongly attenuates the pathogenicity of the virus via induction of typeⅠinterferon[J].Journal of Virology,2015,89(1):312-322.
[15]SAINZ B Jr.,MOSSEL E C,PETERS C J,et al.Interferon-beta and interferon-gamma synergistically inhibit the replication of severe acute respiratory syndrome-associated coronavirus(SARS-CoV)[J].Virology,2004,329(1):11-17.
[16]OKUSE C,RINAUDO J A,FARRAR K,et al.Enhancement of antiviral activity against hepatitis C virus in vitro by interferon combination therapy[J].Antiviral Research,2005,65(1):23-34.
[17]SCHRODER K,HERTZOG P J,RAVASI T,et al.Interferon-γ:an overview of signals,mechanisms and functions[J].Journal of Leukocyte Biology,2004,75(2):163-189.
[18]SOZZANI S,DEL PRETE A,BOSISIO D.Dendritic cell recruitment and activation in autoimmunity[J].Journal of Autoimmunity,2017,85:126-140.
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