NATURALLY-OCCURRING HUMAN PARAINFLUENZA TYPE-3 VIRUSES EXHIBIT DIVERGENCE IN AMINO-ACID-SEQUENCE OF THEIR FUSION PROTEIN NEUTRALIZATION EPITOPES AND CLEAVAGE SITES
NATURALLY-OCCURRING HUMAN PARAINFLUENZA TYPE-3 VIRUSES EXHIBIT DIVERGENCE IN AMINO-ACID-SEQUENCE OF THEIR FUSION PROTEIN NEUTRALIZATION EPITOPES AND CLEAVAGE SITES
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DOI：
10.1128/jvi.64.3.1329-1334.1990
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发表时间：
1990-03-01
影响因子：
5.4
通讯作者：
WINTER, CC
中科院分区：
文献类型：
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作者：
COELINGH, KV;WINTER, CC
从患有呼吸道疾病的儿童中分离的许多人副流感病毒3型（PIV 3）毒株对单克隆抗体（MAb）的中和具有抗性，这些单克隆抗体可识别原型1957 PIV 3毒株融合（F）蛋白抗原位点A或B中的表位。对7株PIV 3临床分离株的F蛋白基因进行测序，以确定它们的中和抗性表型是否与中和单克隆抗体识别的氨基酸特异性差异相关。对位点A或B单克隆抗体中和有抗性的几种临床菌株分别在残基398或73处具有氨基酸差异。这些特定的变化无疑解释了这些分离株的中和抗性表型，因为在单克隆抗体选择的逃逸突变体中，残基398或73处的相同取代赋予了对位点A或B单克隆抗体的中和抗性。在自然发生的和单克隆抗体选择的中和耐药PIV 3毒株中存在相同的变化，这增加了在部分免疫儿童中复制过程中通过免疫选择产生抗原性不同毒株的可能性。检查的7种临床菌株中有3种在其F蛋白裂解位点序列上存在差异。尽管原型PIV 3毒株具有切割位点序列Arg-Thr-Lys-Arg，但一个临床分离株具有序列Arg-Thr-Arg-Arg，两个分离株具有序列Arg-Thr-Glu-Arg。这些病毒的不同裂解位点序列并不影响它们在连续猿猴或牛肾细胞单层（存在或不存在外源性胰蛋白酶或纤溶酶）或恒河猴上呼吸道或下呼吸道中的复制水平。我们得出结论，F蛋白切割位点内的两个非连续碱性残基足以在灵长类动物中有效复制人PIV 3。
Many human parainfluenza type 3 virus (PIV3) strains isolated from children with respiratory illness are resistant to neutralization by monoclonal antibodies (MAbs) which recognize epitopes in antigenic site A or B of the fusion (F) protein of the prototype 1957 PIV3 strain. The F protein genes of seven PIV3 clinical isolates were sequenced to determine whether their neutralization-resistant phenotypes were associated with specific differences in amino acids which are recognized by neutralizing MAbs. Several clinical strains which were resistant to neutralization by site A or B MAbs had amino acid differences at residues 398 or 73, respectively. These specific changes undoubtedly account for the neutralization-resistant phenotype of these isolates, since identical substitutions at residues 398 or 73 in MAb-selected escape mutants confer resistance to neutralization by site A or B MAbs. The existence of identical changes in naturally occurring and MAb-selected neutralization-resistant PIV3 strains raises the possibility that antigenically different strains may arise by immune selection during replication in partially immune children. Three of the seven clinical strains examined had differences in their F protein cleavage site sequence. Whereas the prototype PIV3 strain has the cleavage site sequence Arg-Thr-Lys-Arg, one clinical isolate had the sequence Arg-Thr-Arg-Arg and two isolates had the sequence Arg-Thr-Glu-Arg. The different cleavage site sequences of these viruses did not affect their level of replication in either continuous simian or bovine kidney cell monolayers (in the presence or absence of exogenous trypsin or plasmin) or in the upper or lower respiratory tract of rhesus monkeys. We conclude that two nonconsecutive basic residues within the F protein cleavage site are sufficient for efficient replication of human PIV3 in primates.