猪轮状病毒G9P[13]与人轮状病毒Wa G1P[8]的体外和体内比较研究
Comparative In Vitro and In Vivo Studies of Porcine Rotavirus G9P[13] and Human Rotavirus Wa G1P[8].
作者信息
Shao Lulu, Fischer David D, Kandasamy Sukumar, Rauf Abdul, Langel Stephanie N, Wentworth David E, Stucker Karla M, Halpin Rebecca A, Lam Ham Ching, Marthaler Douglas, Saif Linda J, Vlasova Anastasia N
机构信息
Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, Wooster, Ohio, USA.
J. Craig Venter Institute, Rockville, Maryland, USA.
出版信息
J Virol. 2015 Oct 14;90(1):142-51. doi: 10.1128/JVI.02401-15. Print 2016 Jan 1.
UNLABELLED
The changing epidemiology of group A rotavirus (RV) strains in humans and swine, including emerging G9 strains, poses new challenges to current vaccines. In this study, we comparatively assessed the pathogenesis of porcine RV (PRV) G9P[13] and evaluated the short-term cross-protection between this strain and human RV (HRV) Wa G1P[8] in gnotobiotic pigs. Complete genome sequencing demonstrated that PRV G9P[13] possessed a human-like G9 VP7 genotype but shared higher overall nucleotide identity with historic PRV strains. PRV G9P[13] induced longer rectal virus shedding and RV RNAemia in pigs than HRV Wa G1P[8] and generated complete short-term cross-protection in pigs challenged with HRV or PRV, whereas HRV Wa G1P[8] induced only partial protection against PRV challenge. Moreover, PRV G9P[13] replicated more extensively in porcine monocyte-derived dendritic cells (MoDCs) than did HRV Wa G1P[8]. Cross-protection was likely not dependent on serum virus-neutralizing (VN) antibodies, as the heterologous VN antibody titers in the sera of G9P[13]-inoculated pigs were low. Thus, our results suggest that heterologous protection by the current monovalent G1P[8] HRV vaccine against emerging G9 strains should be evaluated in clinical and experimental studies to prevent further dissemination of G9 strains. Differences in the pathogenesis of these two strains may be partially attributable to their variable abilities to replicate and persist in porcine immune cells, including dendritic cells (DCs). Additional studies are needed to evaluate the emerging G9 strains as potential vaccine candidates and to test the susceptibility of various immune cells to infection by G9 and other common HRV/PRV genotypes.
IMPORTANCE
The changing epidemiology of porcine and human group A rotaviruses (RVs), including emerging G9 strains, may compromise the efficacy of current vaccines. An understanding of the pathogenesis and genetic, immunological, and biological features of the new emerging RV strains will contribute to the development of new surveillance and prevention tools. Additionally, studies of cross-protection between the newly identified emerging G9 porcine RV strains and a human G1 RV vaccine strain in a susceptible host (swine) will allow evaluation of G9 strains as potential novel vaccine candidates to be included in porcine or human vaccines.
未标记
A组轮状病毒（RV）在人和猪中的流行病学变化，包括新出现的G9毒株，给当前疫苗带来了新挑战。在本研究中，我们比较评估了猪RV（PRV）G9P[13]的发病机制，并评估了该毒株与人类RV（HRV）Wa G1P[8]在无菌猪中的短期交叉保护作用。全基因组测序表明，PRV G9P[13]具有类似人类的G9 VP7基因型，但与历史PRV毒株的总体核苷酸同一性更高。与HRV Wa G1P[8]相比，PRV G9P[13]在猪中诱导的直肠病毒脱落和RV血症持续时间更长，并在受到HRV或PRV攻击的猪中产生了完全的短期交叉保护，而HRV Wa G1P[8]仅对PRV攻击诱导了部分保护。此外，PRV G9P[13]在猪单核细胞衍生的树突状细胞（MoDCs）中的复制比HRV Wa G1P[8]更广泛。交叉保护可能不依赖于血清病毒中和（VN）抗体，因为接种G9P[13]的猪血清中的异源VN抗体滴度较低。因此，我们的结果表明，应在临床和实验研究中评估当前单价G1P[8] HRV疫苗对新出现的G9毒株的异源保护作用，以防止G9毒株的进一步传播。这两种毒株发病机制的差异可能部分归因于它们在包括树突状细胞（DCs）在内的猪免疫细胞中复制和持续存在的能力不同。需要进一步研究来评估新出现的G9毒株作为潜在疫苗候选物的可能性，并测试各种免疫细胞对G9和其他常见HRV/PRV基因型感染的易感性。
重要性
猪和人类A组轮状病毒（RV）的流行病学变化，包括新出现的G9毒株，可能会损害当前疫苗的效力。了解新出现的RV毒株的发病机制以及遗传、免疫和生物学特征，将有助于开发新的监测和预防工具。此外，在易感宿主（猪）中研究新鉴定的新出现的G9猪RV毒株与人类G1 RV疫苗毒株之间的交叉保护作用，将有助于评估G9毒株作为潜在新型疫苗候选物纳入猪或人类疫苗的可能性。
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