Increased Virulence of an Epidemic Strain of Vesicular Stomatitis Virus Is Associated With Interference of the Innate Response in Pigs.

Increased Virulence of an Epidemic Strain of Vesicular Stomatitis Virus Is Associated With Interference of the Innate Response in Pigs.
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DOI:
10.3389/fmicb.2018.01891
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发表时间:
2018
影响因子:
5.2
通讯作者:
Rodriguez LL
Rodriguez LL
中科院分区:
生物学2区
文献类型:
--
作者:
Velazquez-Salinas L;Pauszek SJ;Stenfeldt C;O'Hearn ES;Pacheco JM;Borca MV;Verdugo-Rodriguez A;Arzt J;Rodriguez LL

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水泡性口炎病毒(VSV)在美国西南部引起水泡性疾病的零星爆发。与这些暴发相关的流行菌株的内在特征知之甚少。在这项研究中,我们报告了独特的基因组和生物学特性的流行株(NJ 0612 NME 6)的VSV与地方株(NJ 0806 VCB)相比。两种菌株之间的基因组比较显示,共111个核苷酸差异(23个非同义)与潜在相关的替代位于P,G和L蛋白。当在实验感染的猪(VSV的天然宿主)中进行测试时,与感染地方性毒株的猪相比,流行性毒株引起更高的发热和更多的水泡性病变。与感染地方性毒株的猪相比,感染流行性毒株的猪在疾病的急性期表现出降低的全身抗病毒活性(I型- IFN)、较低的抗体水平、较高的白细胞介素6水平和较低的肿瘤坏死因子水平。此外,我们记录了实验感染VSV的猪中存在RNA血症阶段,并探讨了缺乏从血液中回收感染性病毒的原因。最后,流行株被证明是更有效地下调IRF-7在原代猪巨噬细胞的转录。总的来说,数据显示,我们测试的VSV流行株具有增强的调节脊椎动物宿主先天免疫应答的能力。需要进一步的研究,以检查其他流行株,并增加毒力的表型可能有什么贡献VSV在动物流行病的传播。
Vesicular stomatitis virus (VSV) causes sporadic outbreaks of vesicular disease in the southwestern United States. The intrinsic characteristics of epidemic strains associated with these outbreaks are poorly understood. In this study, we report the distinctive genomic and biological characteristics of an epidemic (NJ0612NME6) strain of VSV compared with an endemic (NJ0806VCB) strain. Genomic comparisons between the two strains revealed a total of 111 nucleotide differences (23 non-synonymous) with potentially relevant replacements located in the P, G, and L proteins. When tested in experimentally infected pigs, a natural host of VSV, the epidemic strain caused higher fever and an increased number of vesicular lesions compared to pigs infected with the endemic strain. Pigs infected with the epidemic strain showed decreased systemic antiviral activity (type I – IFN), lower antibody levels, higher levels of interleukin 6, and lower levels of tumor necrosis factor during the acute phase of disease compared to pigs infected with the endemic strain. Furthermore, we document the existence of an RNAemia phase in pigs experimentally infected with VSV and explored the cause for the lack of recovery of infectious virus from blood. Finally, the epidemic strain was shown to be more efficient in down-regulating transcription of IRF-7 in primary porcine macrophages. Collectively, the data shows that the epidemic strain of VSV we tested has an enhanced ability to modulate the innate immune response of the vertebrate host. Further studies are needed to examine other epidemic strains and what contributions a phenotype of increased virulence might have on the transmission of VSV during epizootics.
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