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单点突变可能影响G11型猪轮状病毒株的血清型反应性:范围在扩大?

Single point mutations may affect the serotype reactivity of serotype G11 porcine rotavirus strains: a widening spectrum?

作者信息

Ciarlet M, Hoshino Y, Liprandi F

机构信息

Laboratorio de Biología de Virus, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela.

出版信息

J Virol. 1997 Nov;71(11):8213-20. doi: 10.1128/JVI.71.11.8213-8220.1997.

Abstract

A panel of single and double neutralization-resistant escape mutants of serotype G11 porcine rotavirus strains A253 and YM, selected with G11 monotype- and serotype-specific neutralizing monoclonal antibodies (MAbs) to VP7, was tested in neutralization assays with hyperimmune sera raised against rotavirus strains of different serotypes. Escape mutants with an amino acid substitution in antigenic region A (amino acids [aa] 87 to 101) resulting in a residue identical or chemically similar to those present at the same positions in serotype G3 strains, at positions 87 for strain A253 and 96 for strain YM, were significantly more sensitive than the parental strains to neutralization with sera against some serotype G3 strains. Also, one YM antigenic variant (YM-5E6.1) acquired reactivity by enzyme-linked immunosorbent assay with MAbs 159, 57/8, and YO-1E2, which react with G3 strains, but not with the serotype G11 parental strain YM. Cross-adsorption studies suggested that the observed cross-neutralization by the G3-specific sera was due to the sera containing antibodies reactive with the parental strain plus antibodies reactive with the epitope(s) on the antigenic variant that mimick the serotype G3 specific one(s). Moreover, antibodies reactive with antigenic region F (aa 235 to 242) of VP7 might also be involved since cross-reactivity to serotype G3 was decreased in double mutants carrying an additional mutation, which creates a potential glycosylation site at position 238. Thus, single point mutations can affect the serotype reactivity of G11 porcine rotavirus strains with both monoclonal and polyclonal antibodies and may explain the origin of rotavirus strains with dual serotype specificity based on sequence divergence of VP7.

摘要

用针对轮状病毒VP7的G11单型和血清型特异性中和单克隆抗体(MAb)筛选出的一组G11血清型猪轮状病毒A253和YM株的单中和抗性及双中和抗性逃逸突变体,在针对不同血清型轮状病毒株产生的超免疫血清的中和试验中进行了检测。在抗原区域A(氨基酸[aa]87至101)发生氨基酸取代、导致在G3血清型毒株相同位置出现相同或化学性质相似残基的逃逸突变体,对于A253株为87位,对于YM株为96位,与亲本毒株相比,对一些G3血清型毒株的血清中和作用显著更敏感。此外,一种YM抗原变体(YM - 5E6.1)通过酶联免疫吸附测定获得了与MAb 159、57/8和YO - 1E2的反应性,这些MAb与G3毒株反应,但不与G11血清型亲本毒株YM反应。交叉吸附研究表明,观察到的G3特异性血清的交叉中和作用是由于血清中既含有与亲本毒株反应的抗体,又含有与模拟G3血清型特异性表位的抗原变体上的表位反应的抗体。此外,与VP7抗原区域F(aa 235至242)反应的抗体可能也参与其中,因为在携带额外突变(在238位产生潜在糖基化位点)的双突变体中,与G3血清型的交叉反应性降低。因此,单点突变可影响G11猪轮状病毒株与单克隆抗体和多克隆抗体的血清型反应性,并可能基于VP7的序列差异解释具有双血清型特异性的轮状病毒株的起源。

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