Han Myung Guk, Cheon Doo-Sung, Zhang Xuming, Saif Linda J
Food Animal Health Research Program, Ohio Agricultural Research and Development Center, The Ohio State University, 1680 Madison Avenue, Wooster, OH 44691, USA.
J Virol. 2006 Dec;80(24):12350-6. doi: 10.1128/JVI.00402-06. Epub 2006 Sep 13.
A group 2 human coronavirus designated HECV-4408 was isolated from a child with acute diarrhea and is antigenically and genetically more closely related to bovine coronavirus (BCoV) than to human coronavirus OC43 (X. M. Zhang, W. Herbst, K. G. Kousoulas, and J. Storz, J. Med. Virol. 44:152-161, 1994). To determine whether HECV-4408 infects gnotobiotic calves and induces cross-protective immunity against the virulent enteric BCoV DB2 strain, gnotobiotic calves (n = 4) were orally inoculated with HECV-4408 and then challenged with BCoV DB2 at postinoculation day (PID) 21. All calves inoculated with HECV-4408 developed diarrhea at PID 3 to 4 lasting 5 to 9 days. Fecal and nasal virus shedding were first detected by reverse transcription-PCR at PID 3 to 4 and at PID 2 to 4, respectively. After challenge with bovine coronavirus, no diarrhea or virus shedding was detected in calves inoculated with HECV-4408, but a mock-inoculated calf developed diarrhea and fecal and nasal shedding. Fecal immunoglobulin A (IgA) and serum IgG antibodies were first detected at PID 7 and PID 14, respectively. At postchallenge day 7, serum IgG and fecal IgA antibody titers remained the same or increased only twofold compared to prechallenge titers. An additional two gnotobiotic calves were inoculated with HECV-4408 and euthanized at PID 5. Moderate villous atrophy was observed in the small intestines, and viral antigen was detected in villous enterocytes of the small and large intestines by immunohistochemistry. These results support and extend the previous report that HECV-4408 is likely a variant of bovine coronavirus. They confirm its infectivity for calves and complete cross-protection against a bovine coronavirus (DB2 strain) showing 98.2% amino acid identity to HECV-4408 in the S protein.
从一名急性腹泻儿童中分离出一种2型人冠状病毒，命名为HECV - 4408，在抗原性和基因上，它与牛冠状病毒（BCoV）的关系比与人冠状病毒OC43更为密切（X. M. 张、W. 赫布斯特、K. G. 库索拉斯和J. 斯托兹，《医学病毒学杂志》44:152 - 161, 1994）。为了确定HECV - 4408是否感染无菌犊牛并诱导针对强毒性肠道BCoV DB2株的交叉保护性免疫，对4头无菌犊牛口服接种HECV - 4408，然后在接种后第21天用BCoV DB2进行攻毒。所有接种HECV - 4408的犊牛在接种后第3至4天出现腹泻，持续5至9天。分别在接种后第3至4天和第2至4天通过逆转录 - PCR首次检测到粪便和鼻腔病毒排出。在用牛冠状病毒攻毒后，接种HECV - 4408的犊牛未检测到腹泻或病毒排出，但一头 mock - 接种的犊牛出现腹泻以及粪便和鼻腔病毒排出。粪便免疫球蛋白A（IgA）和血清IgG抗体分别在接种后第7天和第14天首次检测到。在攻毒后第7天，血清IgG和粪便IgA抗体滴度与攻毒前滴度相比保持不变或仅增加两倍。另外两头无菌犊牛接种HECV - 4408并在接种后第5天安乐死。在小肠中观察到中度绒毛萎缩，通过免疫组织化学在小肠和大肠的绒毛肠上皮细胞中检测到病毒抗原。这些结果支持并扩展了先前的报告，即HECV - 4408可能是牛冠状病毒的一个变种。它们证实了其对犊牛的感染性以及对一种在S蛋白中与HECV - 4408具有98.2%氨基酸同一性的牛冠状病毒（DB2株）的完全交叉保护性免疫。
