A Clinical Isolate of Human Parainfluenza Virus 3 (Fukushima/O695/2019) Contains a Mutation in the Serial Guanosines in the RNA Editing Site of the P Gene and Produces an Atypical Number of Nongenomic Guanosine Insertions During RNA Editing

Human parainfluenza virus 3 (HPIV3) contains a purine-rich RNA editing site, allowing multiple viral proteins to be produced from a single gene by the posttranscriptional addition of G nucleotides. The Fukushima/O695/2019 (O695) HPIV3 clinical isolate has a G-to-A substitution at the last position of five serial G residues in the RNA editing site. This study evaluates the effects of this substitution in the RNA editing site on the biological character of HPIV3. Our results show that O695 has slightly reduced viral replication compared with viruses with an intact RNA editing site. The number of G nucleotides inserted into the RNA editing site in HPIV3 isolates with an intact RNA editing site was 5 or fewer in most cases, giving a total of 10 serial G bases (5 + 5). In contrast, the number of G nucleotides inserted into the RNA editing site in O695 showed an atypical pattern, with six or fewer in most cases. This resulted in a total of 10 (4 + 6), suggesting the additional insertion of one more nongenomic G to the mRNA of the P gene of O695 compared with viruses carrying no mutations in the RNA editing site. Phylogenetic analysis reveals that mutations in the RNA editing site occur sporadically with various mutation patterns, suggesting that these mutations are routinely selected for during the life cycle of HPIV3.