Porcine Interferon Stimulated Gene 12a Restricts Porcine Reproductive and Respiratory Syndrome Virus Replication in MARC-145 Cells

Porcine reproductive and respiratory syndrome virus (PRRSV) causes severe losses in the global pig industry. In the present study, we investigated the molecular characterization of porcine interferon stimulated gene 12a (ISG12A) and confirmed its anti-PRRSV ability for the first time. We found that porcine ISG12A was localized in mitochondria and significantly decreased the number of cells in G2/S phase. Porcine ISG12A mRNA was up-regulated in cells/tissues of Tongcheng (TC) pigs and Large White (LW) pigs after PRRSV challenge. More importantly, the ectopic overexpression of ISG12A could significantly suppress PRRSV replication at 24, 36 and 48 h post challenge (hpc), which was confirmed by detecting PRRSV ORF7 mRNA with quantitative reverse transcription polymerase chain reaction (qRT-PCR) and PRRSV N protein with indirect immunofluorescence assay (IFA) in MARC-145 cells. Meanwhile, knockdown of endogenic ISG12A could obviously facilitate PRRSV replication in MARC-145 cells at 36 hpc. The results will lead to a better understanding of the interaction between host immune system and PRRSV, which may help us develop novel therapeutic tools to control PRRSV.

[1]  W. Liang,et al.  2',5'-Oligoadenylate synthetase 1(OAS1) inhibits PRRSV replication in Marc-145 cells. , 2016, Antiviral research.

[2]  R. L. Harrison,et al.  Ratification vote on taxonomic proposals to the International Committee on Taxonomy of Viruses (2016) , 2016, Archives of Virology.

[3]  Lei Xu,et al.  Induction of Apoptosis by the Nonstructural Protein 4 and 10 of Porcine Reproductive and Respiratory Syndrome Virus , 2016, PloS one.

[4]  Xiaohong Wang,et al.  ISG12a Restricts Hepatitis C Virus Infection through the Ubiquitination-Dependent Degradation Pathway , 2016, Journal of Virology.

[5]  W. Liang,et al.  Differences of immune responses between Tongcheng (Chinese local breed) and Large White pigs after artificial infection with highly pathogenic porcine reproductive and respiratory syndrome virus. , 2016, Virus research.

[6]  M. Jacques,et al.  Actinobacillus pleuropneumoniae induces SJPL cell cycle arrest in G2/M-phase and inhibits porcine reproductive and respiratory syndrome virus replication , 2015, Virology Journal.

[7]  G. Bernardini,et al.  NK cells and interferons. , 2015, Cytokine & growth factor reviews.

[8]  B. Liu,et al.  ISG12a mediates cell response to Newcastle disease viral infection. , 2014, Virology.

[9]  Xiaohong Wang,et al.  MiR-942 Mediates Hepatitis C Virus-Induced Apoptosis via Regulation of ISG12a , 2014, PloS one.

[10]  S. Prasanth,et al.  Differential Host Cell Gene Expression and Regulation of Cell Cycle Progression by Nonstructural Protein 11 of Porcine Reproductive and Respiratory Syndrome Virus , 2014, BioMed research international.

[11]  J. Quereda,et al.  Virulence and genotype-associated infectivity of interferon-treated macrophages by porcine reproductive and respiratory syndrome viruses. , 2014, Virus research.

[12]  M. Farago,et al.  The human ISG12a gene is a novel caspase dependent and p53 independent pro-apoptotic gene, that is overexpressed in breast cancer , 2013 .

[13]  Koichiro Tamura,et al.  MEGA6: Molecular Evolutionary Genetics Analysis version 6.0. , 2013, Molecular biology and evolution.

[14]  Jie Liu,et al.  Poly(I:C) inhibits porcine reproductive and respiratory syndrome virus replication in MARC-145 cells via activation of IFIT3. , 2013, Antiviral research.

[15]  E. Snijder,et al.  Nonstructural Protein 2 of Porcine Reproductive and Respiratory Syndrome Virus Inhibits the Antiviral Function of Interferon-Stimulated Gene 15 , 2012, Journal of Virology.

[16]  K. Sudini.  A role for interferon stimulated gene 12a (ISG12a) in vesicular stomatitis virus antiviral responses , 2012 .

[17]  Xiaoping Zhou,et al.  Correction: Molecular Characterization of Transcriptome-wide Interactions between Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus and Porcine Alveolar Macrophages in vivo , 2011, International Journal of Biological Sciences.

[18]  P. Zhou,et al.  Molecular Characterization of Transcriptome-wide Interactions between Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus and Porcine Alveolar Macrophages in vivo , 2011, International journal of biological sciences.

[19]  E. Robertson,et al.  Epstein-Barr Virus Nuclear Antigen 3C Facilitates G1-S Transition by Stabilizing and Enhancing the Function of Cyclin D1 , 2011, PLoS pathogens.

[20]  E. Borden,et al.  Emerging roles of FAM14 family members (G1P3/ISG 6-16 and ISG12/IFI27) in innate immunity and cancer. , 2011, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[21]  Xue-hong Wang,et al.  Influence of Hypericum perforatum Extract on Piglet Infected with Porcine Respiratory and Reproductive Syndrome Virus , 2009 .

[22]  S. Xiao,et al.  Immunogenicity of the highly pathogenic porcine reproductive and respiratory syndrome virus GP5 protein encoded by a synthetic ORF5 gene. , 2009, Vaccine.

[23]  G. Gao,et al.  Porcine Respiratory and Reproductive Syndrome Virus Variants, Vietnam and China, 2007 , 2008, Emerging infectious diseases.

[24]  A. Stella,et al.  Genome-wide transcriptional response of primary alveolar macrophages following infection with porcine reproductive and respiratory syndrome virus , 2008, The Journal of general virology.

[25]  M. Ikeda,et al.  Activation of the cyclin D2 and cdk6 genes through NF-κB is critical for cell-cycle progression induced by HTLV-I Tax , 2008, Oncogene.

[26]  D. Leaman,et al.  Mitochondrial localization and pro-apoptotic effects of the interferon-inducible protein ISG12a , 2008, Apoptosis.

[27]  R. Silverman.  Viral Encounters with 2′,5′-Oligoadenylate Synthetase and RNase L during the Interferon Antiviral Response , 2007, Journal of Virology.

[28]  Di Liu,et al.  Emergence of Fatal PRRSV Variants: Unparalleled Outbreaks of Atypical PRRS in China and Molecular Dissection of the Unique Hallmark , 2007, PloS one.

[29]  Jian Chen,et al.  Genetic Variation of Chinese PRRSV Strains Based on ORF5 Sequence , 2006, Biochemical Genetics.

[30]  J. Ziebuhr,et al.  Nidovirales: Evolving the largest RNA virus genome , 2006, Virus Research.

[31]  Colin D. Johnson,et al.  Assessment of the economic impact of porcine reproductive and respiratory syndrome on swine production in the United States. , 2005, Journal of the American Veterinary Medical Association.

[32]  J. Justesen,et al.  Small ISGs coming forward. , 2004, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[33]  C. Lowenstein,et al.  iNOS (NOS2) at a glance , 2004, Journal of Cell Science.

[34]  A. Porter,et al.  Identification of a novel gene family that includes the interferon-inducible human genes 6–16 and ISG12 , 2004, BMC Genomics.

[35]  H C Thomas,et al.  Polymorphisms in interferon-induced genes and the outcome of hepatitis C virus infection: roles of MxA, OAS-1 and PKR , 2003, Genes and Immunity.

[36]  B. Zhivotovsky,et al.  Mechanisms of Interferon-alpha induced apoptosis in malignant cells , 2002, Oncogene.

[37]  Thomas D. Schmittgen,et al.  Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. , 2001, Methods.

[38]  H. Buttenschøn,et al.  The interferon alpha induced protein ISG12 is localized to the nuclear membrane. , 2001, European journal of biochemistry.

[39]  J. Justesen,et al.  The interferon-induced gene ISG12 is regulated by various cytokines as the gene 6-16 in human cell lines. , 2000, Cytokine.

[40]  K. Rossow.  Porcine Reproductive and Respiratory Syndrome , 1998, Veterinary pathology.

[41]  P. Chambon,et al.  Identification of a new interferon-alpha-inducible gene (p27) on human chromosome 14q32 and its expression in breast carcinoma. , 1993, Cancer research.