Srinivas Mridula Annaswamy, Pierce Linley R, Olson Mikayla C, Roberston Shelly J, Sturdevant Gail L, Best Sonja M, Orchard Robert C
Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Laboratory of Neurological Infections and Immunity, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton MT, USA.
bioRxiv. 2024 Oct 17:2024.10.17.618898. doi: 10.1101/2024.10.17.618898.
Trim7 is an E3 ubiquitin ligase that was recently identified as a central regulator of host-viral interactions with both pro-viral and anti-viral activity in cell culture. As an inhibitor, Trim7 overexpression ubiquitinates viral proteins by recognizing C-terminal glutamines that are hallmarks of 3C-like protease cleavage events. Here we sought to determine the physiological impact of Trim7 in resolving murine norovirus (MNV) infection of mice as MNV is potently inhibited by Trim7 in vitro. Utilizing two independently derived Trim7 deficient mouse lines we found no changes in the viral burden or tissue distribution of MNV in both an acute and persistent model of infection. Additionally, no changes in cytokine responses were observed after acute MNV infection of Trim7-deficient mice. Furthermore, removal of potentially confounding innate immune responses such as STING and STAT1 did not reveal any role for Trim7 in regulating MNV replication. Taken together, our data fails to find a physiological role for Trim7 in regulating MNV infection outcomes in mice and serves as a caution for defining Trim7 as a broad acting antiviral.
Trim7是一种E3泛素连接酶，最近被确定为宿主与病毒相互作用的核心调节因子，在细胞培养中具有促病毒和抗病毒活性。作为一种抑制剂，Trim7的过表达通过识别C端谷氨酰胺来泛素化病毒蛋白，这些谷氨酰胺是3C样蛋白酶切割事件的标志。由于Trim7在体外能有效抑制小鼠诺如病毒（MNV），我们试图确定Trim7在解决小鼠MNV感染中的生理影响。利用两个独立衍生的Trim7缺陷小鼠品系，我们发现在急性和持续性感染模型中，MNV的病毒载量和组织分布均无变化。此外，Trim7缺陷小鼠急性感染MNV后，未观察到细胞因子反应的变化。此外，去除潜在的混杂先天免疫反应，如STING和STAT1，并未揭示Trim7在调节MNV复制中的任何作用。综上所述，我们的数据未能发现Trim7在调节小鼠MNV感染结果中的生理作用，并提醒人们不要将Trim7定义为一种广泛作用的抗病毒药物。
