Abstract：
Water buffalo Hunnivirus (BufHuV) belongs to the family Picornaviridae and is a newly discovered member of the Hunnivirus A genus. It causes intestinal diseases in cattle, mainly lead to subclinical infections, thereby seriously threatening the health of cattle herds. In addition, it can also bring about various clinical disease syndromes which results in severe economic losses to the cattle industry. To date, there have been no reports worldwide on the study of Hunnivirus virus infecting host cells and causing innate immune responses. In this study, we found that interferon treatment effectively blocked BufHuV replication and infection with the virus weakened the host antiviral responses. Inhibiting the transcription of IFN-β and ISGs induced by either Sendai virus (SeV) or poly(I:C) in MDBK and HCT-8 cells, were dependent on the IRF3 or NF-κB signaling pathways, and this inhibited the activation of IFN-β promoter by TBK1 and its upstream molecules, RIGI and MDA5. By constructing and screening five BufHuV proteins, we found that VP2, 2 C, 3 C and 3D inhibited the activation of IFN-β promoter induced by SeV. Subsequently, we showed that VP2 inhibited the activation of IRF3 induced by SeV or poly (I:C), and it inhibited IRF3 activation by inhibiting its phosphorylation and nuclear translocation. In addition, we confirmed that VP2 inhibited the activation of IFNβ induced by signaling molecules, MDA5 and TBKI. In summary, these findings provide new insights into the pathogenesis of Hunnivirus and its mechanisms involved in evading host immune responses.
摘要：
水牛Hunnivirus（BufHuV）属于Picornaviridae家族，是HunnivirusA属的新发现成员。它会导致牛的肠道疾病，主要导致亚临床感染，从而严重威胁牛群的健康。此外,它还可能导致各种临床疾病综合征，从而给养牛业造成严重的经济损失。迄今为止,世界范围内还没有关于流感病毒感染宿主细胞并引起先天免疫反应的研究报告。在这项研究中,我们发现干扰素治疗可有效阻断BufHuV的复制,病毒感染可削弱宿主的抗病毒反应.抑制仙台病毒（SeV）或poly（I：C）在MDBK和HCT-8细胞中诱导的IFN-β和ISGs的转录，依赖于IRF3或NF-κB信号通路，这抑制了TBK1及其上游分子对IFN-β启动子的激活，RIGI和MDA5。通过构建和筛选5个BufHuV蛋白,我们发现VP2，2C，3C和3D抑制SeV诱导的IFN-β启动子的活化。随后，我们表明，VP2抑制了SeV或poly（I：C）诱导的IRF3的激活，它通过抑制其磷酸化和核易位来抑制IRF3的激活。此外,我们证实VP2抑制了信号分子诱导的IFNβ的激活，MDA5和TBKI。总之,这些发现为Hunnivirus的发病机理及其逃避宿主免疫反应的机制提供了新的见解。
