Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
Guangdong Laboratory for Lingnan Modern Agriculture, South China Agricultural University, Guangzhou, China.
Transbound Emerg Dis. 2022 Sep;69(5):e2530-e2540. doi: 10.1111/tbed.14597. Epub 2022 Jun 8.
The Porcine reproductive and respiratory syndrome virus (PRRSV), a single (+) RNA virus, is characterized by high genome variability and constant evolution. Owing to increasingly complex mutations, there is a growing difficulty in accessing the whole genome. Additionally, there is limited knowledge on PRRSV intra-host nucleotide variants, which may reflect the complex viral-host dynamics. Here, we performed next-generation sequencing on four clinical lung tissues to reveal the genomic diversity and highlight virus-host interactions. The complete genomes of the HN0713 and GDYJ1224 strains shared 90.7% and 91.3% homology with the lineage 1 strain NADC30, respectively, while the GDGZ0408 and GDHY0425 strains shared 92.0% and 91.6% homology with the JXA1 strain, respectively. Recombination analysis showed that the ORF5-7 genes of the GDGZ0408 and GDHY0425 strains, whose complete genomes belong to lineage 8.7 based on the phylogenetic tree, are both recombined with lineage 3 strains. Furthermore, nsp3, nsp10-12, ORF2 genes and a part of the 3'-UTR of the GDHY0425 strain were provided by the lineage 5.1 strain. Two lineage 1 strains (GDYJ1224 and HN0713) were produced by a recombination of lineages 8.7 and 1. Additionally, the lineage 3 strain was associated with the recombinant HN0713 strain. We determined the intra-host single nucleotide variant frequencies and found more than 200 sites at a frequency of >1% in all samples. GDGZ0408 with parts of the nsp9 and nsp10 genes of HP-PRRSV lineage 8.7 presented more genetically diverse populations than others, indicating that lineage 8.7 might drive robust intra-host single nucleotide variants (iSNVs). Moreover, in the iSNV pools, nsp2 and ORF2a presented the highest mutation dynamic. Overall, this study provided evidence for the alarmingly increasing recombination and ever-changing evolutionary dynamics of PRRSV, and revealed the potential causes of vaccine escape, providing a novel insight into the nucleotide variant population in clinical samples.
猪繁殖与呼吸综合征病毒（PRRSV）是一种单股正链（+）RNA 病毒，具有高度基因组变异性和持续进化的特点。由于越来越复杂的突变，获取整个基因组变得越来越困难。此外，关于 PRRSV 宿主内核苷酸变异的知识有限，这可能反映了复杂的病毒-宿主动态。在这里，我们对 4 个临床肺组织进行了下一代测序，以揭示基因组多样性并突出病毒-宿主相互作用。HN0713 和 GDYJ1224 株与 1 谱系 NADC30 株的完全基因组同源性分别为 90.7%和 91.3%，而 GDGZ0408 和 GDHY0425 株与 JXA1 株的同源性分别为 92.0%和 91.6%。重组分析表明，GDGZ0408 和 GDHY0425 株的 ORF5-7 基因，其完整基因组基于系统进化树属于 8.7 谱系，均与 3 谱系株重组。此外，GDHY0425 株的 nsp3、nsp10-12、ORF2 基因和部分 3'-UTR 由 5.1 谱系株提供。2 株 1 谱系株（GDYJ1224 和 HN0713）是由 8.7 和 1 谱系重组产生的。此外，3 谱系株与重组 HN0713 株有关。我们确定了宿主内单核苷酸变异频率，在所有样本中发现了 200 多个频率大于 1%的位点。具有部分 nsp9 和 nsp10 基因的 HP-PRRSV 8.7 谱系 GDGZ0408 呈现出比其他谱系更多的遗传多样性群体，表明 8.7 谱系可能驱动强大的宿主内单核苷酸变异（iSNVs）。此外，在 iSNV 池中，nsp2 和 ORF2a 呈现出最高的突变动态。总的来说，本研究为 PRRSV 令人震惊的重组和不断变化的进化动态提供了证据，并揭示了疫苗逃逸的潜在原因，为临床样本中的核苷酸变异群体提供了新的见解。
