Li Dan, Zhu Laixu, Cui Chenchen, Wu Zhenchun, Qing Pengkai, Zhou Qiongqiong, Gao Peng, Zhang Yongning, Zhou Lei, Ge Xinna, Guo Xin, Han Jun, Yang Hanchun
State Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing, China.
Key Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing, China.
Front Microbiol. 2025 Mar 19;16:1563186. doi: 10.3389/fmicb.2025.1563186. eCollection 2025.
Porcine reproductive and respiratory syndrome virus (PRRSV), an economically significant threat to the world pork production, is notoriously known for its heterogeneity, and therefore the current vaccines often fail to provide efficient cross-protection against diverse PRRSV strains.
By making chimeric viruses using HP-PRRSV-2 lineage 8 (JXwn06) and lineage 1 NADC30-like strains (CHsx1401) as model organisms, the recently results have shown that the viral structural protein-coding region is critical for induction of homologous immunity. In this study, the chimeric viruses were further constructed by exchanging the region coding for the minor (GP2/3/4) or major (GP5/M) structural proteins of JXwn06 on the backbone of CHsx1401 to generate two mutants CHsx1401-GP234 and CHsx1401-GP5M.
The subsequent animal experiment showed that all three chimeras could confer good protective immunity against the lethal challenge by HP-PRRSV strain JXwn06, and the survived pigs had much lower lung lesions, faster viremia clearance, and lower viral tissue load. However, the exchange of SP region as a whole performed better than either GP2/3/4 or GP5/M region alone, as the pigs in the latter groups showed transient fever following challenge and higher viral load in certain tissues, highlighting a synergistic role. Interestingly, as compared to the group CHsx1401-GP234, the group CHsx1401-GP5M showed excellent viremia clearance, comparable to the SP group.
Our results in this report revealed the important role of ORFs2-4 and ORFs5-6 regions in induction of protective immunity and have important implications in understanding viral pathogenesis and further vaccine development.
猪繁殖与呼吸综合征病毒(PRRSV)对全球猪肉生产构成重大经济威胁,因其高度异质性而臭名昭著,因此目前的疫苗往往无法对多种PRRSV毒株提供有效的交叉保护。
以HP-PRRSV-2谱系8(JXwn06)和谱系1 NADC30样毒株(CHsx1401)作为模式生物构建嵌合病毒,最近的研究结果表明病毒结构蛋白编码区对诱导同源免疫至关重要。在本研究中,通过在CHsx1401的骨架上交换编码JXwn06次要(GP2/3/4)或主要(GP5/M)结构蛋白的区域,进一步构建嵌合病毒,产生两个突变体CHsx1401-GP234和CHsx1401-GP5M。
随后的动物实验表明,所有三种嵌合体都能对HP-PRRSV毒株JXwn06的致死性攻击提供良好的保护性免疫,存活的猪肺部病变明显减轻,病毒血症清除更快,病毒组织载量更低。然而,作为一个整体的结构蛋白区域交换组比单独的GP2/3/4或GP5/M区域组表现更好,因为后一组的猪在攻毒后出现短暂发热,某些组织中的病毒载量更高,突出了协同作用。有趣的是,与CHsx1401-GP234组相比,CHsx1401-GP5M组表现出优异的病毒血症清除能力,与结构蛋白区域交换组相当。
我们在本报告中的结果揭示了ORFs2-4和ORFs5-6区域在诱导保护性免疫中的重要作用,对理解病毒发病机制和进一步的疫苗开发具有重要意义。