2 DISTINCT HUMAN PARAINFLUENZA VIRUS TYPE-1 GENOTYPES DETECTED DURINGTHE 1991 MILWAUKEE EPIDEMIC

The extent of genetic and antigenic variation found in a population of human parainfluenza virus type 1 (HPIV-1) during a single local epide mic was investigated, Fifteen HPIV-1 strains isolated from children in 1991 were analyzed, Nucleotide sequence variation in the hemagglutini n-neuraminidase protein (HN) gene demonstrated two, distinct genotypes (genotypes C and D), Unique patterns were identified involving 62 nuc leotide and 10 amino acid positions, These patterns represented 40% of all mutations within the HN gene. The remaining mutations were random ly distributed, and 74% involved only one (55%) or two isolates. Genot ypes were statistically different from each other at both the nucleoti de (P = 0.001) and amino acid (P = 0.001) levels and demonstrated uniq ue potential N-linked glycosylation patterns, Thirty-eight monoclonal antibodies (MAbs) made to four different viral proteins (22 HN, 2 fusi on [F]. 1 phosphoprotein, and 13 nucleoprotein) (originating from two different genotypes [genotypes A and D]) were compared for their abili ty to bind to the clinical isolates in enzyme-linked immunosorbent ass ays (ELISAs) and hemagglutinin-inhibition (HI) assays, Twenty-one MAbs bound well to all clinical isolates in ELISAs and HI assays, The rema ining 17 MAbs showed variation in all four structural proteins, Three HN MAbs demonstrated genotype C- and D-specific antigenic and neutrali zation differences, Evolutionary analysis using parsimony methods conf irmed the differences between the two genotypes, No differences In eit her clinical presentation or disease severity between the two genotype s were found, Geographically localized HPIV-1 epidemics can be caused by at least two distinct genotypes with minor but specific antigenic c hanges, The clinical and immunologic roles of HPIV-1 genotypes have no t been determined.