Ward R L, Mason B B, Bernstein D I, Sander D S, Smith V E, Zandle G A, Rappaport R S
Division of Infectious Diseases, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
J Virol. 1997 Aug;71(8):6267-70. doi: 10.1128/JVI.71.8.6267-6270.1997.
The NSP4 protein of a simian rotavirus was reported to induce diarrhea following inoculation of mice. If NSP4 is responsible for rotavirus diarrhea in humans, attenuation of a human rotavirus may be reflected in concomitant mutations in the NSP4 gene. After 33 passages in cultured monkey kidney cells, a virulent human rotavirus (strain 89-12) was found to be attenuated in adults, children, and infants. Nucleotide sequence analysis of the NSP4 protein gene revealed only one base pair change between the virulent (unpassaged) and attenuated 89-12 viruses, which resulted from a substitution of alanine for threonine at amino acid 45 of the encoded NSP4 protein. Because both threonine and alanine have been found at position 45 of NSP4 in symptomatic and asymptomatic human rotaviruses, neither amino acid in this position could be established as a marker of virulence. Therefore, attenuation of rotavirus strain 89-12 appears to be unrelated to mutations in the NSP4 gene.
据报道，猿猴轮状病毒的NSP4蛋白在接种小鼠后会引发腹泻。如果NSP4是人类轮状病毒腹泻的病因，那么人轮状病毒的减毒可能会反映在NSP4基因的伴随突变上。在培养的猴肾细胞中传代33次后，发现一种强毒性人轮状病毒（89 - 12株）在成人、儿童和婴儿中均表现出减毒特性。对NSP4蛋白基因进行核苷酸序列分析发现，强毒性（未传代）89 - 12病毒与减毒后的89 - 12病毒之间仅有一个碱基对的变化，这是由于编码的NSP4蛋白第45位氨基酸处的苏氨酸被丙氨酸取代所致。因为在有症状和无症状的人轮状病毒的NSP4蛋白第45位上都发现了苏氨酸和丙氨酸，所以该位置的任何一种氨基酸都不能被确定为毒力标记。因此，89 - 12轮状病毒株的减毒似乎与NSP4基因的突变无关。
