Distinct hemagglutinin and neuraminidase epitopes involved in antigenic variation of recent human parainfluenza virus type 2 isolates.
A panel of fourteen neutralizing anti-HN monoclonal antibodies (mAbs) to the prototype Greer strain of human parainfluenza virus type 2 (PI2) was used to determine the extent of antigenic variation in recent virus isolates. Competitive binding analysis with the mAbs indicated the presence of at least five distinct antigenic sites (I to V) on the HN glycoprotein molecule. MAbs recognizing different antigenic sites were found to be associated with the hemagglutinin (sites I, IV and V), hemagglutinin and neuraminidase (site II), or neuraminidase (site III) activities. The location of two distinct epitopes identifying the neuraminidase sites (II and III) was further verified from the generation of escape mutants. Antibodies directed to sites I and III failed to show any detectable binding or neutralizing activity against a number of natural PI2 virus isolates collected in Texas between 1986 and 1987. Interestingly, these natural variants, unlike the prototype virus, did not show any detectable neuraminidase activity with fetuin as a substrate and the enzyme activity was only detected with N-acetylneuramin-lactose as an alternative substrate. Despite the observed variation in the antigenic sites, primary infection with the prototype virus or the natural variants generated a protective immune response against challenge infection with the other virus strains.
Ray
R
R
Secretech Inc., Birmingham, AL 35205.
Duncan
J
J
Quinn
R
R
Matsuoka
Y
Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000940:Antigenic Variation; D006224:Cricetinae; D003429:Cross Reactions; D000939:Epitopes; D015707:HN Protein / Q000276:immunology*; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D009439:Neuraminidase / Q000378:metabolism; D009500:Neutralization Tests; D010223:Parainfluenza Virus 2, Human / Q000201:enzymology / Q000276:immunology*; D018184:Paramyxoviridae Infections / Q000276:immunology / Q000382:microbiology
D000911:Antibodies, Monoclonal; D000939:Epitopes; D015707:HN Protein; D009439:Neuraminidase