Cunliffe N A, Woods P A, Leite J P, Das B K, Ramachandran M, Bhan M K, Hart C A, Glass R I, Gentsch J R
Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Department of Health and Human Services, Atlanta, Georgia 30333, USA.
J Med Virol. 1997 Sep;53(1):41-50.
The rotavirus nonstructural glycoprotein NSP4 may represent the first identified viral enterotoxin. We have sequenced reverse transcription-polymerase chain reaction (RT-PCR)-generated fragments of 16 NSP4 genes of human rotavirus (HRV) strains from six different countries, representing seven different G and P type combinations. Based on the amount of sequence divergence between these and 11 previously sequenced NSP4 genes of human and animal rotaviruses, three distinct genetic groups could be recognized. Most strains within a group were closely related to each other at the nucleotide (nt) and amino acid (aa) levels (usually <10% divergence) but more distantly related (maximum 30.0% nt divergence and 24.7% aa divergence) to members of the other groups. Intergroup variation occurred in two highly variable regions of NSP4 (aa 16-34 and aa 131-148). The NSP4 "toxic peptide" (aa 114-135) exhibited aa variation at its carboxy terminus both within and between genetic groups. The largest group (genetic group II) contained HRV strains of subgroup II specificity (including genotypes P[8]G1, P[8]G3, P[6]G3, and P[8]G5 and serotype P8[11]G9), and the smaller group (genetic group I) contained HRV strains of subgroup I specificity (genotype P[4]G2). The NSP4 sequence of the rhesus rotavirus vaccine strain was distinct from all other strains and formed the third group (genetic group III). The NSP4 genes of animal rotaviruses UK, NCDV, and SA11 (genetic group I) and YM (genetic group II) and two possible human-animal rotavirus reassortant strains, Brazilian P[8]G5 and Indian P[11]G9 (genetic group II), could also be classified into one of these groups, suggesting a close evolutionary relationship between human and animal NSP4 genes. These results will facilitate studies of the host immune response to NSP4, which may be relevant to future HRV vaccine design.
轮状病毒非结构糖蛋白NSP4可能是首个被鉴定出的病毒肠毒素。我们对来自六个不同国家的人类轮状病毒（HRV）毒株的16个NSP4基因经逆转录-聚合酶链反应（RT-PCR）产生的片段进行了测序，这些毒株代表了七种不同的G型和P型组合。根据这些序列与之前已测序的11个人类和动物轮状病毒NSP4基因之间的差异程度，可识别出三个不同的遗传组。一个组内的大多数毒株在核苷酸（nt）和氨基酸（aa）水平上彼此密切相关（通常差异<10%），但与其他组的成员关系较远（最大nt差异为30.0%，aa差异为24.7%）。组间变异发生在NSP4的两个高变区（aa 16 - 34和aa 131 - 148）。NSP4“毒性肽”（aa 114 - 135）在其羧基末端在遗传组内和组间均表现出氨基酸变异。最大的组（遗传组II）包含II亚组特异性的HRV毒株（包括基因型P[8]G1、P[8]G3、P[6]G3和P[8]G5以及血清型P8[11]G9），较小的组（遗传组I）包含I亚组特异性的HRV毒株（基因型P[4]G2）。恒河猴轮状病毒疫苗株的NSP4序列与所有其他毒株不同，形成了第三组（遗传组III）。动物轮状病毒UK、NCDV和SA11（遗传组I）以及YM（遗传组II）的NSP4基因，还有两个可能的人-动物轮状病毒重配毒株，巴西P[8]G5和印度P[11]G9（遗传组II），也可归入这些组中的一个，这表明人类和动物NSP4基因之间存在密切的进化关系。这些结果将有助于对宿主针对NSP4的免疫反应进行研究，这可能与未来的HRV疫苗设计相关。
