A novel recombinant porcine reproductive and respiratory syndrome virus with significant variation in cell adaption and pathogenicity

Zhang, Qiaoya; Bai, Juan; Hou, Hefei; Song, Zhongbao; Zhao, Yongxiang; Jiang, Ping

doi:10.1016/j.vetmic.2017.07.028

Cited by 41 publications

(36 citation statements)

References 29 publications

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“…Bootstrap values were calculated using 1,000 replicates. The classifications of subgroups followed those described in previous studies (14)(15)(16)(17)26). To analyze the positions of the two consistently identified amino acid mutations in the spatial structure of NSP9, we predicted the three-dimensional structure of the protein using the I-TASSER online tool (http://zhanglab.ccmb.med.umich.edu/I-TASSER/), as previously described (24), as there is no direct structural information on any of the nidovirus RdRps (27).…”

Section: Cells Antibodies and Virusesmentioning

confidence: 99%

Two Residues in NSP9 Contribute to the Enhanced Replication and Pathogenicity of Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus

Zhao

Gao

Xiong

et al. 2018

J Virol

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Highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) possesses greater replicative capacity and pathogenicity than classical PRRSV. However, the factors that lead to enhanced replication and pathogenicity remain unclear. In our study, an alignment of all available full-length sequences of North American-type PRRSVs ( = 204) revealed two consistent amino acid mutations that differed between HP-PRRSV and classical PRRSV and were located at positions 519 and 544 in nonstructural protein 9. Next, a series of mutant viruses with either single or double amino acid replacements were generated from HP-PRRSV HuN4 and classical PRRSV CH-1a infectious cDNA clones. Deletion of either of the amino acids led to a complete loss of virus viability. In both Marc-145 and porcine alveolar macrophages, the replicative efficiencies of mutant viruses based on HuN4 were reduced compared to the parent, whereas the replication level of CH-1a-derived mutant viruses was increased. Plaque growth assays showed clear differences between mutant and parental viruses. In infected piglets, the pathogenicity of HuN4-derived mutant viruses, assessed through clinical symptoms, viral load in sera, histopathology examination, and thymus atrophy, was reduced. Our results indicate that the amino acids at positions 519 and 544 in NSP9 are involved in the replication efficiency of HP-PRRSV and contribute to enhanced pathogenicity. This study is the first to identify specific amino acids involved in PRRSV replication or pathogenicity. These findings will contribute to understanding the molecular mechanisms of PRRSV replication and pathogenicity, leading to better therapeutic and prognostic options to combat the virus. Porcine reproductive and respiratory syndrome (PRRS), caused by porcine reproductive and respiratory syndrome virus (PRRSV), is a significant threat to the global pig industry. Highly pathogenic PRRSV (HP-PRRSV) first emerged in China in 2006 and has subsequently spread across Asia, causing considerable damage to local economies. HP-PRRSV strains possess a greater replication capacity and higher pathogenicity than classical PRRSV strains, although the mechanisms that underlie these characteristics are unclear. In the present study, we identified two mutations in HP-PRRSV strains that distinguish them from classical PRRSV strains. Further experiments that swapped the two mutations in an HP-PRRSV strain and a classical PRRSV strain demonstrated that they are involved in the replication efficiency of the virus and its virulence. Our findings have important implications for understanding the molecular mechanisms of PRRSV replication and pathogenicity and also provide new avenues of research for the study of other viruses.

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Section: Cells Antibodies and Virusesmentioning

confidence: 99%

Two Residues in NSP9 Contribute to the Enhanced Replication and Pathogenicity of Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus

Zhao

Gao

Xiong

et al. 2018

J Virol

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“…More importantly, lineage 3 viruses with greater virulence have been reported in southern China, and these viruses, recombined with HP‐PRRSV (lineage 8.7, JXA1‐like), would pose a great threat to the Chinese pig industry (Dong et al, ; Zhang et al, ). Previous knowledge of lineage 3 viruses was limited because only a few strains had been isolated.…”

Section: Discussionmentioning

confidence: 99%

“…Threats of lineage 3 viruses to pig farming have increased, and these viruses co‐circulating with other PRRSVs are frequently detected in vaccinated farm animals. Consequently, the more pathogenic lineage 3 viruses recombined with HP‐PRRSVs have emerged and caused extensive outbreaks in different regions in south China as reported (Dong et al, ; Zhang et al, ). Here, the origin, epidemic history, changes in population, transmission routes and high‐risk areas of lineage 3 viruses were explored globally.…”

Section: Introductionmentioning

confidence: 96%

“…Epidemiological studies reported that lineage 3 viruses are endemic in China from some time (Cao et al, ; Wang et al, ; Xie et al, ; Yin et al, ). Recent evidence states that novel lineage 3 viruses with increased virulence emerged in south China (Dong et al, ; Zhang et al, ). We previously reported the prevalence of lineage 3 viruses to be 35.68% (95% CI: 27.6%–44.3%) in south China, similar to that of the Chinese high‐pathogenic PRRSV (HP‐PRRSV; lineage 8.7) of 54.19% (95% CI: 47.5%–60.8%) (Sun et al, ).…”

Section: Introductionmentioning

confidence: 99%

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Phylogeography, phylodynamics and the recent outbreak of lineage 3 porcine reproductive and respiratory syndrome viruses in China

Sun

Han

Wei

et al. 2019

Transbound Emerg Dis

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Novel highly pathogenic porcine reproductive and respiratory syndrome viruses (PRRSVs) have attracted increasing attention owing to their continual high emergence and recent re‐emergence. Recently, lineage 3 PRRSVs, belonging to the type 2 viruses, with novel characteristics and increased virulence have been continuously re‐emerging in China, thereby posing a great threat to pig farming. However, available information about lineage 3 is limited. Here, we carried out molecular epidemiological investigations for PRRSV surveillance in most regions of China from 2007 to 2017. More than 3,000 samples were obtained, amounting to 73 sequences of lineage 3 viruses. The origin, demographic history and spread pattern of lineage 3 PRRSVs were investigated combining with the database globally. Phylogeography and phylodynamic analyses within a Bayesian statistical framework revealed that lineage 3 viruses originated in Taiwan. Followed by subsequent propagation to different areas and geography, it dichotomized into two endemic clusters. South China has become an epicentre for these viruses, which diffused into China's interiors in recent years. Furthermore, viral dispersal route analysis revealed the risk of viral diffusion. Overall, the origin, epidemic history and geographical evolution of lineage 3 PRRSVs were comprehensively analysed in this study. In particular, the epicentre of southern China and the diffusion routines of the viruses are highlighted in this study, and the possible continuous transmission of the novel lineages poses the biggest threat to pig farmers.

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“…Resulting recombinants contribute to genetic variations and evolution of PRRSV. Some of the PRRSV recombinants exhibit enhanced pathogenicity (Kwon et al, 2019;Zhang et al, 2017;Zhao et al, 2015). PRRSV recombinants may reduce protective efficacies of vaccines and also bring a difficulty to epidemiologic monitoring.…”

Section: Distribution Of Prrsv Recombinants Is Wide Geographically Imentioning

confidence: 99%

Molecular and Cellular Mechanisms for PRRSV Pathogenesis and Host Response to Infection

et al. 2020

Virus Research

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A novel recombinant porcine reproductive and respiratory syndrome virus with significant variation in cell adaption and pathogenicity

Cited by 41 publications

References 29 publications

Two Residues in NSP9 Contribute to the Enhanced Replication and Pathogenicity of Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus

Two Residues in NSP9 Contribute to the Enhanced Replication and Pathogenicity of Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus

Phylogeography, phylodynamics and the recent outbreak of lineage 3 porcine reproductive and respiratory syndrome viruses in China

Molecular and Cellular Mechanisms for PRRSV Pathogenesis and Host Response to Infection

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