ORF5 of porcine reproductive and respiratory syndrome virus (PRRSV) is a target of diversifying selection as infection progresses from acute infection to virus rebound

Chen, Nanhua; Trible, Benjamin R.; Kerrigan, Maureen; Tian, Kegong; Rowland, Raymond R. R.

doi:10.1016/j.meegid.2016.03.002

Cited by 40 publications

(44 citation statements)

References 67 publications

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“…These sites are located in the GP5 ectodomain, and variation at these positions can alter GP5 peptide signal processing or N -linked glycosylation [6,7,16,59]. In addition, a recent study identified these positions as sites of diversifying selection early after PRRSV infection [60], suggesting these sites may be targets of immune selection. However, amino acid substitutions A27 and/or N32 in GP5 were present in both neutralization-resistant and neutralization-sensitive ORF2–6 haplotypes (Figure 3), indicating that variation at these sites was not predictive of neutralization phenotype.…”

Section: Discussionmentioning

confidence: 99%

Antigenic and Biological Characterization of ORF2–6 Variants at Early Times Following PRRSV Infection

Evans

Loyd

Dunkelberger

et al. 2017

Viruses

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Genetic diversity of porcine reproductive and respiratory syndrome virus (PRRSV) challenges efforts to develop effective and broadly acting vaccines. Although genetic variation in PRRSV has been extensively documented, the effects of this variation on virus phenotype are less well understood. In the present study, PRRSV open reading frame (ORF)2–6 variants predominant during the first six weeks following experimental infection were characterized for antigenic and replication phenotype. There was limited genetic variation during these early times after infection; however, distinct ORF2–6 haplotypes that differed from the NVSL97-7895 inoculum were identified in each of the five pigs examined. Chimeric viruses containing all or part of predominant ORF2–6 haplotypes were constructed and tested in virus neutralization and in vitro replication assays. In two pigs, genetic variation in ORF2–6 resulted in increased resistance to neutralization by autologous sera. Mapping studies indicated that variation in either ORF2–4 or ORF5–6 could confer increased neutralization resistance, but there was no single amino acid substitution that was predictive of neutralization phenotype. Detailed analyses of the early steps in PRRSV replication in the presence and absence of neutralizing antibody revealed both significant inhibition of virion attachment and, independently, a significant delay in the appearance of newly synthesized viral RNA. In all pigs, genetic variation in ORF2–6 also resulted in significant reduction in infectivity on MARC-145 cells, suggesting variation in ORF2–6 may also be important for virus replication in vivo. Together, these data reveal that variation appearing early after infection, though limited, alters important virus phenotypes and contributes to antigenic and biologic diversity of PRRSV.

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Section: Discussionmentioning

confidence: 99%

Antigenic and Biological Characterization of ORF2–6 Variants at Early Times Following PRRSV Infection

Evans

Loyd

Dunkelberger

et al. 2017

Viruses

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“…The data of rectal temperature, virus load, antibody level and weight gain were shown in means ± standard deviations ( SD ). The differences between groups were determined by Mann–Whitney U test using GraphPad Prism version 6.07 (Chen, Trible, Kerrigan, Tian, & Rowland, ; Chen, Dekkers, Ewen, & Rowland, ). A p value < 0.05 was considered statistically significant.…”

Section: Methodsmentioning

confidence: 99%

Emergence of a novel highly pathogenic recombinant virus from three lineages of porcine reproductive and respiratory syndrome virus 2 in China 2017

Chen

et al. 2018

Transbound Emerg Dis

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A novel porcine reproductive and respiratory syndrome virus 2 (PRRSV2) was isolated from diseased piglets in Shandong, China in 2017 and denominated as SD17-38. ORF5 sequencing showed that SD17-38 contains a unique serine/asparagine deletion at position 33 and an asparagine insertion at position 60 of GP5, which has never been described. The SD17-38 complete genome was then determined, and genome-based phylogenetic analysis showed that SD17-38 is clustered with NADC30-like isolates. Sequence alignment and recombination analyses by RDP4 and SimPlot all indicated that SD17-38 is a recombinant virus from NADC30 (lineage 1), BJ-4 (lineage 5) and TJ (lineage 8) isolates. Animal challenge study in 4-week piglets showed that SD17-38 causes high fever (≥41°C), 100% morbidity and 40% mortality. In addition, significantly lower weight gain and severe histopathological lung lesions could be observed in SD17-38-infected pigs. In particular, the unique deletion and insertion in GP5 were stable during the challenge study. This study provides direct evidence for the natural occurrence of recombination events among three lineages of PRRSV2 in Chinese swine herds, resulting in the emergence of novel PRRSV variant with unique genetic property and high pathogenicity.

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“…A same pair of multiplex identifier (MID) primers was used for the three amplicons in the second round of PCR. The amplicon library was created by these three amplicons as we previously described [ 25 , 26 ].…”

Section: Methodsmentioning

confidence: 99%

Deep Sequencing Details the Cross-over Map of Chimeric Genes in Two Porcine Reproductive and Respiratory Syndrome Virus Infectious Clones

2017

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ORF5 of porcine reproductive and respiratory syndrome virus (PRRSV) is a target of diversifying selection as infection progresses from acute infection to virus rebound

Cited by 40 publications

References 67 publications

Antigenic and Biological Characterization of ORF2–6 Variants at Early Times Following PRRSV Infection

Antigenic and Biological Characterization of ORF2–6 Variants at Early Times Following PRRSV Infection

Emergence of a novel highly pathogenic recombinant virus from three lineages of porcine reproductive and respiratory syndrome virus 2 in China 2017

Deep Sequencing Details the Cross-over Map of Chimeric Genes in Two Porcine Reproductive and Respiratory Syndrome Virus Infectious Clones

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