Yuan Lijuan, Honma Shinjiro, Ishida Shin-Ichi, Yan Xiao-Yi, Kapikian Albert Z, Hoshino Yasutaka
Epidemiology Section, Laboratory of Infectious Disease, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Virology. 2004 Dec 5;330(1):92-104. doi: 10.1016/j.virol.2004.09.021.
Using recombinant baculoviruses expressing rotavirus NSP4 [A], [B], [C], and [D] genotypes of bovine, porcine, human, simian, or murine origin, we analyzed serum antibody responses to NSP4s in gnotobiotic calves and piglets infected by the oral/alimentary or intraamniotic route with bovine (NSP4[A]) (Wyatt, R.G., Mebus, C.A., Yolken, R.H., Kalica, A.R., James, H.D., Jr., Kapikian, A.Z., Chanock, R.M., 1979. Rotaviral immunity in gnotobiotic calves: heterologous resistance to human virus induced by bovine virus. Science 203(4380), 548-550) or porcine (NSP4[B]) (Hoshino, Y., Saif, L.J., Sereno, M.M., Chanock, R.M., Kapikian, A.Z., 1988. Infection immunity of piglets to either VP3 or VP7 outer capsid protein confers resistance to challenge with a virulent rotavirus bearing the corresponding antigen. J. Virol. 62(3), 744-748) rotaviruses. Following primary infection and challenge with virulent rotaviruses, the animals developed higher or significantly higher antibody titers to homologous host homotypic NSP4s than to heterologous host homotypic or heterologous host heterotypic NSP4s, indicating that antibody responses were species specific rather than genotype specific. Antibody responses to NSP4s corresponded closely with the phylogenetic relationships of NSP4s within a species-specific region of amino acids (aa) 131-141. In contrast, NSP4 genotypes determined by amino acid full-length sequence identity predicted poorly their "serotypes". In piglets, antibodies to NSP4 induced by previous oral infection failed to confer protection against challenge from a porcine rotavirus bearing serotypically different VP4 and VP7 but essentially identical NSP4 to the porcine rotavirus in primary infection. Thus, in an approach to immunization with a live oral rotavirus vaccine, the NSP4 protein does not appear to play an important role in protection against rotavirus disease and infection.
利用表达牛、猪、人、猴或鼠源轮状病毒NSP4 [A]、[B]、[C]和[D]基因型的重组杆状病毒，我们分析了通过口服/经消化道或羊膜内途径感染牛（NSP4[A]）（Wyatt, R.G., Mebus, C.A., Yolken, R.H., Kalica, A.R., James, H.D., Jr., Kapikian, A.Z., Chanock, R.M., 1979. 无菌小牛的轮状病毒免疫：牛病毒诱导的对人病毒的异源抗性。《科学》203(4380), 548 - 550）或猪（NSP4[B]）（Hoshino, Y., Saif, L.J., Sereno, M.M., Chanock, R.M., Kapikian, A.Z., 1988. 仔猪对VP3或VP7外衣壳蛋白的感染免疫赋予对携带相应抗原的强毒轮状病毒攻击的抗性。《病毒学杂志》62(3), 744 - 748）轮状病毒的无菌小牛和仔猪对NSP4s的血清抗体反应。在初次感染并用强毒轮状病毒攻击后，动物对同源宿主同型NSP4s产生的抗体滴度高于对异源宿主同型或异源宿主异型NSP4s产生的抗体滴度，或显著更高，这表明抗体反应具有种属特异性而非基因型特异性。对NSP4s的抗体反应与氨基酸（aa）131 - 141物种特异性区域内NSP4s的系统发育关系密切对应。相比之下，由氨基酸全长序列同一性确定的NSP4基因型对其“血清型”的预测效果较差。在仔猪中，先前口服感染诱导的针对NSP4的抗体未能对携带血清型不同的VP4和VP7但与初次感染中的猪轮状病毒NSP4基本相同的猪轮状病毒攻击提供保护。因此，在使用口服活轮状病毒疫苗进行免疫的方法中，NSP4蛋白似乎在预防轮状病毒疾病和感染方面不起重要作用。
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