Osman Rahwa, Gonzalez-Cano Patricia, Brownlie Robert, Griebel Philip J
School of Public Health, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5A8, Canada.
Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5E3, Canada.
J Gen Virol. 2017 Jul;98(7):1831-1842. doi: 10.1099/jgv.0.000825. Epub 2017 Jul 5.
Invitro investigations have identified a variety of mechanisms by which herpesviruses evade interferon-stimulated antiviral effector mechanisms. However, these immune evasion mechanisms have not been evaluated during a bovine herpesvirus-1 (BHV-1) infection. This study investigated the transcription and secretion of type I and II interferons (IFNs) and the transcription of IFN-stimulated genes (ISGs) during a primary BHV-1 infection of the upper respiratory tract (URT) in naïve calves. IFN-α, -β and -γ transcription in nasal turbinates and protein levels in nasal secretions increased following infection. Increased IFN type I and II secretion was detected 3 days post-infection (p.i.) and IFN production increased in parallel with virus shedding. Expression of ISGs, including Mx1, OAS and BST-2, also increased significantly (P<0.05) in nasal turbinates on day 3 p.i. and elevated ISG expression persisted throughout the period of viral shedding. In contrast, RNAase L gene expression was not induced during the BHV-1 infection in the nasal turbinates, but was induced on day 10 p.i. in the trachea. In vitro studies confirmed that recombinant bovine (rBo)IFN-α, -β and -γ induced expression of Mx1, OAS and BST-2, but decreased RNAse L transcript in bovine epithelial cells. Relative to vesicular stomatitisvirus (VSV), BHV-1 was resistant to the antiviral activity of rBoIFN-α and -γ, but treatment of epithelial cells with 10 ng rBoIFN-β ml-1 effected an 80 % inhibition of BHV-1 replication and complete inhibition of VSV replication. These observations confirm that the transcription and translation of type I and II IFNs increase during BHV-1 infection, while the transcription of some ISGs is not inhibited.
体外研究已经确定了疱疹病毒逃避干扰素刺激的抗病毒效应机制的多种机制。然而，这些免疫逃避机制尚未在牛疱疹病毒1型（BHV-1）感染期间进行评估。本研究调查了初乳期犊牛上呼吸道（URT）原发性BHV-1感染期间I型和II型干扰素（IFN）的转录和分泌以及干扰素刺激基因（ISG）的转录。感染后，鼻甲中IFN-α、-β和-γ的转录以及鼻分泌物中的蛋白质水平增加。感染后3天（p.i.）检测到I型和II型IFN分泌增加，并且IFN产生与病毒脱落平行增加。包括Mx1、OAS和BST-2在内的ISG的表达在感染后第3天在鼻甲中也显著增加（P<0.05），并且ISG表达升高在病毒脱落期间持续存在。相比之下，鼻甲中的BHV-1感染期间未诱导RNA酶L基因表达，但在感染后第10天在气管中诱导表达。体外研究证实，重组牛（rBo）IFN-α、-β和-γ诱导牛上皮细胞中Mx1、OAS和BST-2的表达，但降低RNA酶L转录本。相对于水疱性口炎病毒（VSV），BHV-1对rBoIFN-α和-γ的抗病毒活性具有抗性，但用10 ng rBoIFN-β ml-1处理上皮细胞可实现对BHV-1复制的80%抑制和对VSV复制的完全抑制。这些观察结果证实，在BHV-1感染期间I型和II型IFN的转录和翻译增加，而一些ISG的转录未被抑制。
