Stability of the Parainfluenza Virus 5 Genome Revealed by Deep Sequencing of Strains Isolated from Different Hosts and following Passage in Cell Culture

Abstract

The strain diversity of a rubulavirus, parainfluenza virus 5 (PIV5), was investigated by comparing 11 newly determined and 6 previously published genome sequences. These sequences represent 15 PIV5 strains, of which 6 were isolated from humans, 1 was from monkeys, 2 were from pigs, and 6 were from dogs. Strain diversity is remarkably low, regardless of host, year of isolation, or geographical origin; a total of 7.8% of nucleotides are variable, and the average pairwise difference between strains is 2.1%. Variation is distributed unevenly across the PIV5 genome, but no convincing evidence of selection for antibody-mediated evasion in hemagglutinin-neuraminidase was found. The finding that some canine and porcine, but not primate, strains are mutated in the SH gene, and do not produce SH, raised the possibility that dogs (or pigs) may not be the natural host of PIV5. The genetic stability of PIV5 was also demonstrated during serial passage of one strain (W3) in Vero cells at a high multiplicity of infection, under conditions of competition with large proportions of defective interfering genomes. A similar observation was made for a strain W3 mutant (PIV5VΔC) lacking V gene function, in which the dominant changes were related to pseudoreversion in this gene. The mutations detected in PIV5VΔC during pseudoreversion, and also those characterizing the SH gene in canine and porcine strains, predominantly involved U-to-C transitions. This suggests an important role for biased hypermutation via an adenosine deaminase, RNA-specific (ADAR)-like activity.IMPORTANCE Here we report the sequence variation of 16 different isolates of parainfluenza virus 5 (PIV5) that were isolated from a number of species, including humans, monkeys, dogs, and pigs, over 4 decades. Surprisingly, strain diversity was remarkably low, regardless of host, year of isolation, or geographical origin. Variation was distributed unevenly across the PIV5 genome, but no convincing evidence of immune or host selection was found. This overall genome stability of PIV5 was also observed when the virus was grown in the laboratory, and the genome stayed remarkably constant even during the selection of virus mutants. Some of the canine isolates had lost their ability to encode one of the viral proteins, termed SH, suggesting that although PIV5 commonly infects dogs, dogs may not be the natural host for PIV5.

Measles Virus Defective Interfering RNAs Are Generated Frequently and Early in the Absence of C Protein and Can Be Destabilized by Adenosine Deaminase Acting on RNA-1-Like Hypermutations

“…These unencapsidated DI-RNAs may be the doublestranded RNA that elicits innate immune responses in negativestrand RNA virus infections. ADAR1 A-to-I editing has also been documented in full-length RNA virus genomes (33,34,60,61) and was recently inferred by deep sequencing analyses of several paramyxoviruses (62,63).…”

Aetiology of Canine Infectious Respiratory Disease Complex and Prevalence of its Pathogens in Europe

“…CPiV belongs to the family Paramyxoviridae, subfamily Rubulavirinae, comprising also distantly related human parainfluenza viruses 2 and 4, and mumps virus (reviewed by Ellis and Krakowa, 2012;ICTV, 2018). Although the virus is generally still referred to as CPiV in veterinary medicine, the correct nomenclature evolved from 'parainfluenza virus 5' (Rima et al, 2014) to 'mammalian orthorubulavirus 5', and this name is consistent with the isolation of the virus from various mammals, including man and dogs (ICTV, 2018). The virus is highly contagious and therefore endemic worldwide.…”

Arenavirus Quasispecies and Their Biological Implications

“…Hypermutation has been related to posttranscriptional editing by host adenosine deaminases of viral genomes from persistent infections of other RNA viruses such as measles virus (Cattaneo and Billeter 1992), human parainfluenza virus (Murphy et al 1991;Rima et al 2014), and respiratory syncytial viruses (Rueda et al 1994). In these studies, the estimated mutation frequencies of U → C or A → G transitions were in the range of 3.3 × 10 −2 to 1.0 × 10 −1 mutations per nucleotide.…”