Naturally occurring human parainfluenza type 3 viruses exhibit divergence in amino acid sequence of their fusion protein neutralization epitopes and cleavage sites.
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.
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
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Coelingh
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Winter
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002648:Child; D000939:Epitopes / Q000235:genetics*; D005814:Genes, Viral; D014644:Genetic Variation; D006801:Humans; D008253:Macaca mulatta; D009500:Neutralization Tests; D010224:Parainfluenza Virus 3, Human / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D012141:Respiratory Tract Infections / Q000382:microbiology; D018108:Respirovirus / Q000235:genetics*; D014760:Viral Fusion Proteins / Q000235:genetics* / Q000276:immunology; D015678:Viral Structural Proteins / Q000235:genetics; D014779:Virus Replication
D000939:Epitopes; D014760:Viral Fusion Proteins; D015678:Viral Structural Proteins