Department of Ophthalmology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Department of Biology, East Texas Baptist University, Marshall, TX 75670, USA.
Viruses. 2022 Mar 12;14(3):589. doi: 10.3390/v14030589.
Tripartite-motif 21 (TRIM21) is thought to regulate the type I interferon (IFN) response to virus pathogens and serve as a cytosolic Fc receptor for immunoglobulin. Since herpes simplex virus (HSV)-1 is sensitive to type I IFN and neutralizing antibody, we investigated the role of TRIM21 in response to ocular HSV-1 infection in mice. In comparison to wild type (WT) mice, TRIM21 deficient (TRIM21 KO) mice were found to be no more susceptible to ocular HSV-1 infection than WT animals, in terms of infectious virus recovered in the cornea. Similar pathology, in terms of neovascularization, opacity, and loss of peripheral vision function, was observed in both WT and TRIM21 KO mice. However, TRIM21 KO mice did possess a significant increase in infectious virus recovered in the trigeminal ganglia, in comparison to the WT animals. The increased susceptibility was not due to changes in HSV-1-specific CD4+ or CD8+ T cell numbers or functional capabilities, or in changes in type I IFN or IFN-inducible gene expression. In summary, the absence of TRIM21 results in a modest, but significant, increase in HSV-1 titers recovered from the TG of TRIM21 KO mice during acute infection, by a mechanism yet to be determined.
三结构域蛋白 21（TRIM21）被认为可以调节对病毒病原体的 I 型干扰素（IFN）反应，并作为免疫球蛋白的细胞质 Fc 受体。由于单纯疱疹病毒（HSV）-1 对 I 型 IFN 和中和抗体敏感，因此我们研究了 TRIM21 在小鼠眼 HSV-1 感染中的作用。与野生型（WT）小鼠相比，TRIM21 缺陷（TRIM21 KO）小鼠在角膜中回收的感染性病毒方面，与 WT 动物相比，对眼 HSV-1 感染的敏感性没有更高，在新生血管形成、混浊和周边视力丧失方面，WT 和 TRIM21 KO 小鼠均表现出相似的病理学。然而，与 WT 动物相比，TRIM21 KO 小鼠在三叉神经节中回收的感染性病毒确实显著增加。与 WT 动物相比，增加的易感性不是由于 HSV-1 特异性 CD4+或 CD8+T 细胞数量或功能能力的变化，也不是由于 I 型 IFN 或 IFN 诱导基因表达的变化。总之，在急性感染期间，TRIM21 的缺失导致从 TRIM21 KO 小鼠的 TG 中回收的 HSV-1 滴度适度但显著增加，其机制尚待确定。
