Amino acid variation within the fusion protein of respiratory syncytial virus subtype A and B strains during annual epidemics in South Africa
Amino acid variation within the fusion protein of respiratory syncytial virus subtype A and B strains during annual epidemics in South Africa
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DOI：
10.1007/s11262-004-5633-2
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发表时间：
2005-03-01
期刊：
影响因子：
1.6
通讯作者：
Venter, M
中科院分区：
文献类型：
--
作者：
Agenbach, E;Tiemessen, CT;Venter, M
最近的证据表明，流感病毒高度保守的核蛋白的细胞毒性T细胞（CTL）表位内的正选择提出了一个问题，即呼吸道合胞病毒（RSV）的CTL表位是否也受到每年流行的免疫驱动变化的影响。RSV的融合蛋白（F蛋白）在两种亚型（A和B）中高度保守，并且是保护性反应的最重要靶点。各种中和表位的位置已经在RSV亚型之间作图和表征。CTL表位最近也被映射为亚型A的F-蛋白，然而这些表位之间和亚型内的变化尚未确定。为了解决这一问题，对在南非5年内鉴定的代表所有亚组A和B基因型的18种菌株的F蛋白进行测序。F-蛋白序列高度保守的内部和南非基因型之间，与大多数变异发生在核苷酸水平。中和和CTL表位内鉴定的大多数氨基酸差异在亚型内是保守的，因此不表明免疫选择。然而，在先前在A亚型中鉴定的三个CTL表位中，两个（限于HLA B* 57和HLA A * 01）仅在A亚型中保守，而第三个（限于Cw* 12）包含亚型和基因型特异性变化。这些结果表明，大多数鉴定的CTL表位是A亚型特异性的，并且可能在B亚型病毒中不被识别，而HLA Cw* 12限制性表位在GA 5株中也可能不被有效识别。
Recent evidence of positive selection within the cytotoxic T-cell (CTL) epitopes of the highly conserved nucleoprotein of influenza virus raised the question of whether the CTL epitopes of Respiratory syncytial virus (RSV) are also affected by immune driven change over annual epidemics. The fusion protein (F-protein) of RSV is highly conserved within the two subtypes ( A and B) and the most important target for the protective response. The position of various neutralizing epitopes has been mapped and characterized between RSV subtypes. CTL epitopes have also recently been mapped for the F-protein of subtype A, however variation within these epitopes between and within the subtypes has not been determined. To address this question, the F-proteins of 18 strains representative of all subgroup A and B genotypes identified in South Africa over a period of 5 years were sequenced. F-protein sequences were highly conserved within and between South African genotypes, with most variability occurring at the nucleotide level. Most of the amino acid differences identified within neutralizing and CTL epitopes were conserved within the subtypes, and therefore does not indicate immune selection. However, out of three CTL epitopes previously identified in subtype A, two ( restricted to HLA B* 57 and HLA A * 01) were conserved only within subtype A, while the third ( restricted to Cw* 12) contained both subtype- and genotype-specific changes. These results suggest that most of the identified CTL epitopes are subtype A-specific and may not be recognized in subtype B viruses, while the HLA Cw* 12 restricted epitope may also not be recognized efficiently in GA5 strains.