Evolutionary Dynamics of Type 2 Porcine Reproductive and Respiratory Syndrome Virus by Whole-Genome Analysis

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV), an important pathogen in the swine industry, is a genetically highly diverse RNA virus. However, the phylogenetic and genomic recombination properties of this virus are not yet fully understood. In this study, we performed an integrated analysis of all available whole-genome sequences of type 2 PRRSV (n = 901) to reveal its evolutionary dynamics. The results showed that there were three distinct phylogenetic lineages of PRRSV in their distribution patterns. We identified that sublineage 2.7 (L2.7), associated with a NADC30 cluster, had the highest substitution rate and higher viral genetic diversity, and inter-lineage recombination is observed more frequently in L2.7 PRRSV compared to other sublineages. Most inter-lineage recombination events detected are observed between L2.7 PRRSVs (as major parents) and L3.4 (a JXA1-R-related cluster)/L3.7 (a WUH3-related cluster) PRRSVs (as minor parents). Moreover, the recombination hotspots are located in the structural protein gene ORF2 and ORF4, or in the non-structural protein gene nsp7. In addition, a GM2-related cluster, L3.2, shows inconsistent recombination modes compared to those of L2.7, suggesting that it may have undergone extensive and unique recombination in their evolutionary history. We also identified several amino acids under positive selection in GP2, GP4 and GP5, the major glycoproteins of PRRSV, showing the driving force behind adaptive evolution. Taken together, our results provide new insights into the evolutionary dynamics of PPRSV that contribute to our understanding of the critical factors involved in its evolution and guide future efforts to develop effective preventive measures against PRRSV.

Attenuated Porcine Reproductive and Respiratory Syndrome Virus Regains Its Fatal Virulence by Serial Passaging in Pigs or Porcine Alveolar Macrophages To Increase Its Adaptation to Target Cells

“…These data indicated that not only the four reverse mutation sites but also some other sites mutated during in vitro reverse passaging (see Table S2 in the supplemental material) may contribute to the adaptation to PAMs and the reobtained fatal virulence of the viruses. So positive selection site identification ( 41 – 43 ) and AlphaFold protein structure prediction ( 44 , 45 ) might be used to further screen the candidate sites among the genomes in our future study.…”

Using Alphafold2 to Predict the Structure of the Gp5/M Dimer of Porcine Respiratory and Reproductive Syndrome Virus

“…We also predicted the structures of the Gp5/M of viruses belonging to four different sublineages of PRRSV-2 [ 61 ]. The results, displayed in Figure S6 , revealed that the folding of each dimer was consistent with the predicted structure of the Gp5/M of VR 2332.…”

“…We also predicted the signal peptide cleavage sites of the Gp5 of the representative members of the three clades of the PRRSV-2 strains and their sublineages [ 61 ]. Every Gp5 protein had the main cleavage site between residue 31 and 32, but for 10 of the 15 sequences, a second minor site upstream of the main site was predicted.…”

“…For structure predictions we used amino acid sequences from the prototype PRRSV-1 strain Lelystad (GenBank: M96262.2) and the prototype PRRSV-2 strain VR 2332 (AY150564.1), lineage 2.1. For structure predictions of the representative members of four other PRRSV-2 lineages [ 61 ], we used the amino acid sequences of isolate HK2, lineage 2.2, KF287133.1; isolate MN414, lineage 2.6, KT581982.1; strain CH-1a, lineage 3.1, AY032626.1; and strain WUH3, lineage 3.7, HM853673.2 in the case of Gp5 without their signal peptides. Since signal peptides are usually rapidly cleaved after the translocation of the protein into the lumen of the ER, they are unlikely to affect protein folding.…”

Special Issue “State-of-the-Art Porcine Virus Research in China”

“…The original studies mainly focus on the pathogenicity, evolution, and detection of porcine reproductive and respiratory syndrome virus (PRRSV), coronaviruses, and circoviruses, which are the top porcine viruses circulating in China to date [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. As reported, PRRSV regulates the expression of poly- N -acetyllactosamine and complex N -glycan in porcine pulmonary microvascular endothelial cells [ 1 ].…”