Pathogenic Characterization of European Genotype Porcine Reproductive and Respiratory Syndrome Virus Recently Isolated in Mainland China

Background:Porcine reproductive and respiratory syndrome virus (PRRSV) is an important pathogen in pig that causes tremendous economic loss in the global swine industry. PRRSV is divided into the European and North American genotypes, with virulence ranging from apathogenic-moderately virulent to highly pathogenic. The emergence of new highly virulent type 1 strains and coexistence of the two genotypes complicate the differential diagnosis, disease prevention, and control of PRRSV. Although the emergence of a novel type 1 PRRSV strain in mainland China was first confirmed in 2011, there is no information available concerning the pathogenesis of this strain.Objectives:We sought to determine the pathogenesis of a newly emerged Chinese type 1 PRRSV strain HLJB1.Methods:Pigs were infected with HLJB1 and characterized using serological and histopathological tests.Results:HLJB1 infection induced transient chemosis, reddened conjunctiva, skin cyanosis, mild transient pyrexia, dyspnea, and tachypnea between 7 and 13 days post-infection. Gross pneumonic lesions were characterized by multifocal, tan-mottled areas. Lymph nodes and spleen were enlarged. Characteristic microscopic lesions consisted of pulmonary consolidation and alveolar septal thickening with red blood cell infiltration, depletion of splenic lymphocytes, and hyperplasia and activation of macrophage. No pigs infected with HLJB1 died during the experiment.Conclusion:Our findings indicate that Chinese type I PRRSV strain HLJB1 caused classic PRRSV-specific lesions. As it caused lower viremia in pigs compared with other classic type 1 isolates, HLJB1 is less virulent than other type I strains.

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PRV UL13 inhibits cGAS–STING-mediated IFN-β production by phosphorylating IRF3

Veterinary Research ◽

10.1186/s13567-020-00843-4 ◽

2020 ◽

Vol 51 (1) ◽

Author(s):

Zongyi Bo ◽

Yurun Miao ◽

Rui Xi ◽

Qiuping Zhong ◽

Chenyi Bao ◽

...

Keyword(s):

Transcriptional Activation ◽

Pseudorabies Virus ◽

Nuclear Translocation ◽

Economic Loss ◽

Inhibitory Effect ◽

Poly I:C ◽

Interferon Response ◽

Type I ◽

Creb Binding Protein ◽

Swine Industry

Abstract Cyclic GMP-AMP (cGAMP) synthase (cGAS) is an intracellular sensor of cytoplasmic viral DNA created during virus infection, which subsequently activates the stimulator of interferon gene (STING)-dependent type I interferon response to eliminate pathogens. In contrast, viruses have developed different strategies to modulate this signalling pathway. Pseudorabies virus (PRV), an alphaherpesvirus, is the causative agent of Aujeszky’s disease (AD), a notable disease that causes substantial economic loss to the swine industry globally. Previous reports have shown that PRV infection induces cGAS-dependent IFN-β production, conversely hydrolysing cGAMP, a second messenger synthesized by cGAS, and attenuates PRV-induced IRF3 activation and IFN-β secretion. However, it is not clear whether PRV open reading frames (ORFs) modulate the cGAS–STING-IRF3 pathway. Here, 50 PRV ORFs were screened, showing that PRV UL13 serine/threonine kinase blocks the cGAS–STING-IRF3-, poly(I:C)- or VSV-mediated transcriptional activation of the IFN-β gene. Importantly, it was discovered that UL13 phosphorylates IRF3, and its kinase activity is indispensable for such an inhibitory effect. Moreover, UL13 does not affect IRF3 dimerization, nuclear translocation or association with CREB-binding protein (CBP) but attenuates the binding of IRF3 to the IRF3-responsive promoter. Consistent with this, it was discovered that UL13 inhibits the expression of multiple interferon-stimulated genes (ISGs) induced by cGAS–STING or poly(I:C). Finally, it was determined that PRV infection can activate IRF3 by recruiting it to the nucleus, and PRVΔUL13 mutants enhance the transactivation level of the IFN-β gene. Taken together, the data from the present study demonstrated that PRV UL13 inhibits cGAS–STING-mediated IFN-β production by phosphorylating IRF3.

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Structural comparison of CD163 SRCR5 from different species sheds some light on its involvement in porcine reproductive and respiratory syndrome virus-2 infection in vitro

Veterinary Research ◽

10.1186/s13567-021-00969-z ◽

2021 ◽

Vol 52 (1) ◽

Author(s):

Hongfang Ma ◽

Rui Li ◽

Longguang Jiang ◽

Songlin Qiao ◽

Xin-xin Chen ◽

...

Keyword(s):

Scavenger Receptor ◽

Host Cells ◽

Respiratory Syndrome Virus ◽

Swine Industry ◽

Prrs Virus ◽

Rich Domain ◽

Serious Disease ◽

The One ◽

And Control

AbstractPorcine reproductive and respiratory syndrome (PRRS) is a serious disease burdening global swine industry. Infection by its etiological agent, PRRS virus (PRRSV), shows a highly restricted tropism of host cells and has been demonstrated to be mediated by an essential scavenger receptor (SR) CD163. CD163 fifth SR cysteine-rich domain (SRCR5) is further proven to play a crucial role during viral infection. Despite intense research, the involvement of CD163 SRCR5 in PRRSV infection remains to be elucidated. In the current study, we prepared recombinant monkey CD163 (moCD163) SRCR5 and human CD163-like homolog (hCD163L1) SRCR8, and determined their crystal structures. After comparison with the previously reported crystal structure of porcine CD163 (pCD163) SRCR5, these structures showed almost identical structural folds but significantly different surface electrostatic potentials. Based on these differences, we carried out mutational research to identify that the charged residue at position 534 in association with the one at position 561 were important for PRRSV-2 infection in vitro. Altogether the current work sheds some light on CD163-mediated PRRSV-2 infection and deepens our understanding of the viral pathogenesis, which will provide clues for prevention and control of PRRS.

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Porcine 2′,5′-oligoadenylate synthetase-like protein inhibits replication of porcine reproductive and respiratory syndrome virus

10.21203/rs.2.18823/v1 ◽

2019 ◽

Author(s):

huawei li ◽

ruining wang ◽

wenjia wang ◽

yinfeng kang ◽

mengmeng zhao

Keyword(s):

Alveolar Macrophages ◽

Respiratory Syndrome Virus ◽

Type I ◽

Oligoadenylate Synthetase ◽

Swine Industry ◽

Exogenous Expression ◽

Polymerase Chain ◽

Interfering Rna ◽

Inducible Gene

Abstract Background : Porcine reproductive and respiratory syndrome virus (PRRSV) is a serious pathogen that causes $664 million losses per year to the swine industry. There are few useful vaccines that can provide protection against PRRSV infection. 2′, 5′-oligoadenylate synthetase-like protein (OASL) has antiviral activity, this has not been shown for PRRSV and the mechanism is unknown. Methods : Expression of OASL in porcine alveolar macrophages induced by interferon (IFN)-b stimulation and PRRSV infection was examined by real-time polymerase chain reaction. Exogenous expression and knockdown of OASL were used to determine the role of OASL in the PRRSV replication cycle. The type I IFN signaling pathway was evaluated after OASL overexpression. Results : In this study, we found that the expression of OASL in porcine alveolar macrophages was significantly increased by IFN-b stimulation and PRRSV infection. Porcine-OASL-specific small interfering RNA (siRNA) promoted PRRSV replication, whereas exogenous expression of porcine OASL inhibited replication of the virus. The anti-PRRSV activity of porcine OASL was lost after knockdown of retinoic acid-inducible gene I ( DDX58 , also known as RIG-I ). Conclusions : Porcine OASL suppresses PRRSV replication.

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PRRSV Vaccine Strain-Induced Secretion of Extracellular ISG15 Stimulates Porcine Alveolar Macrophage Antiviral Response against PRRSV

Viruses ◽

10.3390/v12091009 ◽

2020 ◽

Vol 12 (9) ◽

pp. 1009

Author(s):

Hongbin Liu ◽

Bingjun Shi ◽

Zhigang Zhang ◽

Bao Zhao ◽

Guangming Zhao ◽

...

Keyword(s):

Monoclonal Antibody ◽

Vaccine Strain ◽

Sandwich Elisa ◽

Respiratory Syndrome Virus ◽

Enzyme Linked Immunosorbent Assay ◽

Porcine Alveolar Macrophage ◽

Type I ◽

Swine Industry ◽

Host Interactions ◽

Isg15 Expression

Porcine reproductive and respiratory syndrome virus (PRRSV) has disrupted the global swine industry since the 1980s. PRRSV-host interactions are largely still unknown but may involve host ISG15 protein. In this study, we developed a monoclonal antibody (Mab-3D5E6) specific for swine ISG15 (sISG15) by immunizing mice with recombinant sISG15. A sandwich enzyme-linked immunosorbent assay (ELISA) incorporating this sISG15-specific Mab was developed to detect sISG15 and provided a lower limit of sISG15 detection of 200 pg/mL. ELISA results demonstrated that infection of porcine alveolar macrophages (PAMs) with low-virulence or attenuated PRRSV vaccine strains induced intracellular ISG15 expression that was independent of type I IFN production, while PAMs infection with a PRRSV vaccine strain promoted extracellular ISG15 secretion from infected PAMs. Conversely, the addition of recombinant sISG15 to PAMs mimicked natural extracellular ISG15 effects whereby sISG15 functioned as a cytokine by activating PAMs. Once activated, PAMs could inhibit PRRSV replication and resist infection with PRRSV vaccine strain TJM. In summary, a sandwich ELISA incorporating homemade anti-ISG15 Mab detected ISG15 secretion induced by PAMs infection with a PRRSV vaccine strain. Recombinant ISG15 added to cells exhibited cytokine-like activity that stimulated PAMs to assume an anti-viral state that enabled them to inhibit PRRSV replication and resist viral infection.

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Identification of Two Porcine Reproductive and Respiratory Syndrome Virus Variants Sharing High Genomic Homology but with Distinct Virulence

Viruses ◽

10.3390/v11090875 ◽

2019 ◽

Vol 11 (9) ◽

pp. 875 ◽

Cited By ~ 4

Author(s):

Nanhua Chen ◽

Mengxue Ye ◽

Yucheng Huang ◽

Shuai Li ◽

Yanzhao Xiao ◽

...

Keyword(s):

Amino Acid ◽

Control Strategies ◽

Economic Loss ◽

Respiratory Syndrome Virus ◽

Amino Acid Deletion ◽

Swine Industry ◽

Sequence Alignments ◽

Genetic Feature ◽

Pathogenic Analysis ◽

Highly Virulent

Porcine reproductive and respiratory syndrome virus (PRRSV) causes huge economic loss to the global swine industry. Even though several control strategies have been applied, PRRS is still not effectively controlled due to the continuous emergence of new variants and limited cross-protection by current vaccines. During the routine epidemiological investigation in 2017, two PRRSV variants were identified from a severe abortion farm and a clinically healthy farm, respectively. The viruses were isolated and denominated as XJ17-5 and JSTZ1712-12. Genomic sequencing indicated that their genomes are both 14,960 bp in length sharing 99.45% nucleotide identity. Sequence alignments identified a discontinuous 30-amino-acid deletion and a continuous 120-amino-acid deletion in nsp2 of both isolates. Genome-based phylogenetic analysis confirmed that XJ17-5 and JSTZ1712-12 belong to the HP-PRRSV subtype but form a new branch with other isolates containing the same 150-amino-acid deletion in nsp2. Pathogenic analysis showed that XJ17-5 is highly virulent causing 60% mortality, while JSTZ1712-12 is avirulent for piglets. Furthermore, fragment comparisons identified 34-amino-acid differences between XJ17-5 and JSTZ1712-12 that might be associated with the distinct virulence. The identification of highly homologous HP-PRRSV variants with new genetic feature and distinct virulence contributes to further analyze the pathogenesis and evolution of PRRSV in the field.

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Comparative pathogenesis of type 1 (European genotype) and type 2 (North American genotype) porcine reproductive and respiratory syndrome virus in infected boar

Virology Journal ◽

10.1186/1743-422x-10-156 ◽

2013 ◽

Vol 10 (1) ◽

pp. 156 ◽

Cited By ~ 7

Author(s):

Kiwon Han ◽

Hwi Seo ◽

Changhoon Park ◽

Yeonsu Oh ◽

Ikjae Kang ◽

...

Keyword(s):

North American ◽

Respiratory Syndrome Virus ◽

North American Genotype ◽

European Genotype

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Evasion of Antiviral Innate Immunity by Porcine Reproductive and Respiratory Syndrome Virus

Frontiers in Microbiology ◽

10.3389/fmicb.2021.693799 ◽

2021 ◽

Vol 12 ◽

Author(s):

Tong-Yun Wang ◽

Ming-Xia Sun ◽

Hong-Liang Zhang ◽

Gang Wang ◽

Guoqing Zhan ◽

...

Keyword(s):

Innate Immunity ◽

Immune Responses ◽

Viral Infections ◽

Respiratory Syndrome Virus ◽

Type I ◽

Swine Industry ◽

Interferon Stimulated Genes ◽

Β Receptor ◽

Underlying Mechanisms ◽

Antiviral Innate Immunity

Innate immunity is the front line for antiviral immune responses and bridges adaptive immunity against viral infections. However, various viruses have evolved many strategies to evade host innate immunity. A typical virus is the porcine reproductive and respiratory syndrome virus (PRRSV), one of the most globally devastating viruses threatening the swine industry worldwide. PRRSV engages several strategies to evade the porcine innate immune responses. This review focus on the underlying mechanisms employed by PRRSV to evade pattern recognition receptors signaling pathways, type I interferon (IFN-α/β) receptor (IFNAR)-JAK-STAT signaling pathway, and interferon-stimulated genes. Deciphering the antiviral immune evasion mechanisms by PRRSV will enhance our understanding of PRRSV’s pathogenesis and help us to develop more effective methods to control and eliminate PRRSV.

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Porcine Reproductive and Respiratory Syndrome Virus Antagonizes PCSK9’s Antiviral Effect via Nsp11 Endoribonuclease Activity

Viruses ◽

10.3390/v12060655 ◽

2020 ◽

Vol 12 (6) ◽

pp. 655

Author(s):

Yujiao Zhang ◽

Fei Gao ◽

Liwei Li ◽

Kuan Zhao ◽

Shan Jiang ◽

...

Keyword(s):

Antiviral Activity ◽

Alveolar Macrophages ◽

Antiviral Effect ◽

Respiratory Syndrome Virus ◽

Nonstructural Proteins ◽

Swine Industry ◽

Virus Receptor ◽

Endoribonuclease Activity

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important pathogens in the swine industry worldwide. Our previous study had indicated that proprotein convertase subtilisin/kexin type 9 (PCSK9) was a responsive gene in porcine alveolar macrophages (PAMs) upon PRRSV infection. However, whether PCSK9 impacts the PRRSV replication and how the PRRSV modulates host PCSK9 remains elusive. Here, we demonstrated that PCSK9 protein suppressed the replication of both type-1 and type-2 PRRSV species. More specifically, the C-terminal domain of PCSK9 was responsible for the antiviral activity. Besides, we showed that PCSK9 inhibited PRRSV replication by targeting the virus receptor CD163 for degradation through the lysosome. In turn, PRRSV could down-regulate the expression of PCSK9 in both PAMs and MARC-145 cells. By screening the nonstructural proteins (nsps) of PRRSV, we showed that nsp11 could antagonize PCSK9’s antiviral activity. Furthermore, mutagenic analyses of PRRSV nsp11 revealed that the endoribonuclease activity of nsp11 was critical for antagonizing the antiviral effect of PCSK9. Collectively, our data provide further insights into the interaction between PRRSV and the cell host and offer a new potential target for the antiviral therapy of PRRSV.

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