Molecular cloning and sequence analysis of human parainfluenza type 4A virus HN gene: its irregularities on structure and activities.

We cloned the cDNA of human parainfluenza type 4A virus (PIV-4A) HN gene by reverse-transcription of virus-specific mRNAs and genomic RNA, and determined the complete nucleotide sequence of the HN gene. The predicted HN protein sequence of PIV-4A showed significant relatedness with those of other paramyxoviruses, SV5, NDV, MuV, PIV-3, BPIV-3, indicating a common ancestor. The homologies between the viruses suggested that PIV-4A is more closely related to NDV, SV5, and MuV than to the parainfluenza viruses, PIV-3, bovine parainfluenza type 3 virus (BPIV-3), and Sendai virus (SV). Sixty amino acids were commonly conserved among the viruses, other than PIV-4A. Two of these amino acids were substituted in PIV-4A HN and are predicted to be located near the active site of the neuraminidase. The analysis of neuraminidase of PIV-4 revealed that the activity is hardly detectable, suggesting the significant effect of the substituted amino acid sites on neuraminidase activity.