TY - JOUR

T1 - Stability of the parainfluenza virus 5 genome revealed by deep sequencing of strains isolated from different hosts and following passage in cell culture

AU - Rima, Bert K.

AU - Gatherer, Derek

AU - Young, Daniel F.

AU - Norsted, Hannah

AU - Randall, Richard E.

AU - Davison, Andrew J.

N1 - Copyright © 2014 Rima et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 3.0 Unported license.

PY - 2014/4

Y1 - 2014/4

N2 - The strain diversity of a rubulavirus, parainfluenza virus 5 (PIV5), was investigated by comparing 11 newly determined and six previously published genome sequences. These sequences represent 15 PIV5 strains, of which six were isolated from humans, one from monkeys, two from pigs, and six 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 the haemagglutinin-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 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 on the sequence variation of 17 different isolates of parainfluenza virus type 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 dogs 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.

AB - The strain diversity of a rubulavirus, parainfluenza virus 5 (PIV5), was investigated by comparing 11 newly determined and six previously published genome sequences. These sequences represent 15 PIV5 strains, of which six were isolated from humans, one from monkeys, two from pigs, and six 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 the haemagglutinin-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 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 on the sequence variation of 17 different isolates of parainfluenza virus type 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 dogs 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.

U2 - 10.1128/JVI.03351-13

DO - 10.1128/JVI.03351-13

M3 - Journal article

C2 - 24453358

VL - 88

SP - 3826

EP - 3836

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 7

ER -