Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, The Queen's University of Belfast, Belfast, United Kingdom.
J Virol. 2014 Apr;88(7):3826-36. doi: 10.1128/JVI.03351-13. Epub 2014 Jan 22.
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.
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.
通过比较 11 个新确定的和 6 个已发表的基因组序列，研究了副粘病毒 5（PIV5）的株系多样性。这些序列代表了 15 株 PIV5 株，其中 6 株分离自人类，1 株分离自猴子，2 株分离自猪，6 株分离自狗。无论宿主、分离年份还是地理位置如何，株系多样性都非常低；核苷酸的总变异性为 7.8%，株间平均差异为 2.1%。变异在整个 PIV5 基因组中分布不均匀，但在血凝素-神经氨酸酶中未发现针对抗体介导逃逸的选择的令人信服的证据。发现一些犬科和猪科，而不是灵长类动物的株系在 SH 基因中发生突变，并且不产生 SH，这提出了这样一种可能性，即狗（或猪）可能不是 PIV5 的天然宿主。在高感染复数下，在与大量缺陷干扰基因组竞争的情况下，通过在vero 细胞中连续传代一株（W3）也证明了 PIV5 的遗传稳定性。在缺乏 V 基因功能的 PIV5VΔC 株突变体中也观察到了类似的观察结果，其中主要的变化与该基因的假回复有关。在 PIV5VΔC 中在假回复期间检测到的突变，以及表征犬科和猪科株系中的 SH 基因的突变，主要涉及 U 到 C 的转换。这表明通过腺苷脱氨酶，RNA 特异性（ADAR）样活性，偏向性高突变起着重要作用。
在这里，我们报告了来自多个物种（包括人类、猴子、狗和猪）的 16 种不同的副流感病毒 5（PIV5）分离株的序列变异，这些分离株跨越了 4 个十年。令人惊讶的是，无论宿主、分离年份还是地理位置如何，株系多样性都非常低。变异在整个 PIV5 基因组中分布不均匀，但未发现免疫或宿主选择的令人信服的证据。当病毒在实验室中生长时，PIV5 的这种整体基因组稳定性也得到了观察，即使在选择病毒突变体时，基因组也保持着惊人的稳定性。一些犬科分离株已失去了编码一种病毒蛋白（称为 SH）的能力，这表明尽管 PIV5 通常感染狗，但狗可能不是 PIV5 的天然宿主。
