The nsp2 Hypervariable Region of Porcine Reproductive and Respiratory Syndrome Virus Strain JXwn06 Is Associated with Viral Cellular Tropism to Primary Porcine Alveolar Macrophages.
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TLDR
A mutant of the Chinese highly pathogenic PRRSV strain JXwn06 carrying a deletion spanning nsp2 amino acids 323 to 521 in its hypervariable region was found to lose infectivity in primary porcine alveolar macrophages (PAMs), although it could replicate relatively efficiently in the supporting cell line MARC-145.Abstract:
Porcine reproductive and respiratory syndrome virus (PRRSV) poses a major threat to global pork production and has been notorious for its rapid genetic evolution in the field. The nonstructural protein 2 (nsp2) replicase protein represents the fastest evolving region of PRRSV, but the underlying biological significance has remained poorly understood. By deletion mutagenesis, we discovered that the nsp2 hypervariable region plays an important role in controlling the balance of genomic mRNA and a subset of subgenomic mRNAs. More significantly, we revealed an unexpected link of the nsp2 hypervariable region to viral tropism. Specifically, a mutant of the Chinese highly pathogenic PRRSV strain JXwn06 carrying a deletion spanning nsp2 amino acids 323 to 521 (nsp2Δ323-521) in its hypervariable region was found to lose infectivity in primary porcine alveolar macrophages (PAMs), although it could replicate relatively efficiently in the supporting cell line MARC-145. Consequently, this mutant failed to establish an infection in piglets. Further dissection of the viral life cycle revealed that the mutant had a defect (or defects) lying in the steps between virus penetration and negative-stranded RNA synthesis. Taken together, our results reveal novel functions of nsp2 in the PRRSV life cycle and provide important insights into the mechanisms of PRRSV RNA synthesis and cellular tropism.IMPORTANCE The PRRSV nsp2 replicase protein undergoes rapid and broad genetic variations in its middle region in the field, but the underlying significance has remained enigmatic. Here, we demonstrate that the nsp2 hypervariable region not only plays an important regulatory role in maintaining the balance of different viral mRNA species but also regulates PRRSV tropism to primary PAMs. Our results reveal novel functions for PRRSV nsp2 and have important implications for understanding the mechanisms of PRRSV RNA synthesis and cellular tropism.read more
Citations
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The Novel PRRSV Strain HBap4-2018 with a Unique Recombinant Pattern Is Highly Pathogenic to Piglets.
Pengfei Chen,Xiangmei Tan,Mengqin Lao,Xia Wu,Xiongwei Zhao,Shuting Zhou,Jiarong Yu,Junrui Zhu,Lingxue Yu,Wu Tong,Fei Gao,Hai Yu,Changlong Liu,Yifeng Jiang,Guangzhi Tong,Yanjun Zhou +15 more
TL;DR: In this paper, a porcine reproductive and respiratory syndrome virus (PRRSV) strain named HBap4-2018 was isolated from swine herds suffering severe respiratory disease with high morbidity in Hebei Province of China.
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Porcine Reproductive and Respiratory Syndrome Virus Reverse Genetics and the Major Applications
TL;DR: The approaches to construct an infectious cDNA for PRRSV and the ten major applications of these infectious clones are described to study virus biology and virus–host interaction, and to design a new generation of vaccines with improved levels of safety and efficacy.
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Porcine Reproductive and Respiratory Syndrome Virus Utilizes Viral Apoptotic Mimicry as an Alternative Pathway To Infect Host Cells.
TL;DR: This study demonstrated that PRRSV externalized phosphatidylserine on the envelope as viral apoptotic mimicry and infected host cells through T-cell immunoglobulin and mucin domain (TIM)-induced and CD163-involved macropinocytosis as an alternative pathway.
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The jigsaw of PRRSV virulence
Inés Ruedas-Torres,Irene M. Rodríguez-Gómez,Jose María Sánchez-Carvajal,F. Larenas-Muñoz,F.J. Pallarés,Librado Carrasco,Jaime Gómez-Laguna +6 more
TL;DR: In this paper, a review of the characteristics and differences in clinical signs, lesions, viral replication and tropism between virulent and classical PRRSV strains and a first approximation to the criteria to define a virulent strain was proposed.
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Porcine Reproductive and Respiratory Syndrome Virus Interferes with Swine Influenza A Virus Infection of Epithelial Cells.
Georges Saade,Déborah Ménard,Caroline Hervet,Patricia Renson,Erika Hue,Jianzhong Zhu,Laurence Dubreil,Romain Paillot,Stéphane Pronost,Olivier Bourry,Gaëlle Simon,Joëlle Dupont,Nicolas Bertho,François Meurens +13 more
TL;DR: It is shown for the first time that PRRSV can alter the relation between swIAV and its main target cells, opening the doors to further studies on the interplay between viruses.
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