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轮状病毒的抗原性受VP7的基因背景和糖基化作用影响。

Rotavirus antigenicity is affected by the genetic context and glycosylation of VP7.

作者信息

Lazdins I, Coulson B S, Kirkwood C, Dyall-Smith M, Masendycz P J, Sonza S, Holmes I H

机构信息

School of Microbiology, University of Melbourne, Parkville, Victoria, Australia.

出版信息

Virology. 1995 May 10;209(1):80-9. doi: 10.1006/viro.1995.1232.

DOI:10.1006/viro.1995.1232
PMID:7747487
Abstract

Rotavirus variants resistant to neutralization were selected using monoclonal antibodies (N-MAbs) raised to VP7 of rotavirus G types 2, 3, and 6. Their neutralization resistance patterns and deduced VP7 amino acid sequences were obtained. Variants selected by two G2-specific N-MAbs from the homologous parent virus RV-5 showed single amino acid (aa) mutations in the antigenic A region. However, variants selected from reassortant virus RV-5 x SA11 (all genes from SA11 virus except that encoding VP7, which was from RV-5 virus) fell into two neutralization resistance groups. The first group showed identical mutations to the variants selected from RV-5 virus. The second group showed antigenic C region mutations, either alone or in combination with a mutation at aa 69. Variants selected from G3 parent viruses glycosylated at position 238 had a mutation at aa 96 in the A region, otherwise a C-region mutation at 211 was selected. Mutations at amino acid positions 94 or 96 were selected by monoclonal antibodies specific for each of the three serotypes. G3-specific monoclonal antibodies also selected mutations at position 148 and the new position of 264. This latter mutation resulted in substitution of aspartic acid for glycine and was located in a highly conserved and hydrophobic region of VP7. A G2-specific N-MAb selected variants with a mutation at aa 190 producing a new, utilized glycosylation site which we propose to be in new antigenic site E. The positions of mutations in antigenic variants and their antigenicity were determined by parental background genes and VP7 glycosylation.

摘要

使用针对轮状病毒G2、G3和G6型VP7产生的单克隆抗体(N-MAbs)筛选出对中和作用具有抗性的轮状病毒变体。获得了它们的中和抗性模式和推导的VP7氨基酸序列。从同源亲本病毒RV-5中通过两种G2特异性N-MAbs筛选出的变体在抗原A区域显示出单个氨基酸(aa)突变。然而,从重组病毒RV-5 x SA11(除编码VP7的基因来自RV-5病毒外,所有基因均来自SA11病毒)中筛选出的变体分为两个中和抗性组。第一组显示出与从RV-5病毒中筛选出的变体相同的突变。第二组显示出抗原C区域突变,单独出现或与第69位氨基酸处的突变一起出现。从在第238位糖基化的G3亲本病毒中筛选出的变体在A区域的第96位氨基酸处有突变,否则在第211位筛选出C区域突变。针对三种血清型各自的单克隆抗体在第94或96位氨基酸处筛选出突变。G3特异性单克隆抗体还在第148位和新的第264位筛选出突变。后一个突变导致天冬氨酸取代甘氨酸,位于VP7高度保守的疏水区域。一种G2特异性N-MAb筛选出在第190位氨基酸处有突变的变体,产生了一个新的、可利用的糖基化位点,我们认为该位点位于新的抗原位点E。抗原变体中的突变位置及其抗原性由亲本背景基因和VP7糖基化决定。

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