Center for Neurobiology and Vaccine Development, Ophthalmology Research, Department of Surgery, Cedars-Sinai Burns and Allen Research Institute, Los Angeles, California, USA.
J Virol. 2024 Mar 19;98(3):e0201023. doi: 10.1128/jvi.02010-23. Epub 2024 Feb 20.
Herpes simplex virus-1 (HSV-1) infections are among the most frequent serious viral eye infections in the U.S. and are a major cause of viral-induced blindness. HSV-1 infection is known to induce T cell activation, proliferation, and differentiation that play crucial roles in the development of virus-induced inflammatory lesions, leading to eye disease and causing chronic corneal damage. CD80 is a co-stimulatory molecule and plays a leading role in T cell differentiation. Previous efforts to limit lesion severity by controlling inflammation at the cellular level led us to ask whether mice knocked out for CD80 would show attenuated virus replication following reactivation. By evaluating the effects of CD80 activity on primary and latent infection, we found that in the absence of CD80, virus replication in the eyes and virus reactivation in latent trigeminal ganglia were both significantly reduced. However, latency in latently infected CD80 mice did not differ significantly from that in wild-type (WT) control mice. Reduced virus replication in the eyes of CD80 mice correlated with significantly expanded CD11c gene expression as compared to WT mice. Taken together, our results indicate that suppression of CD80 could offer significant beneficial therapeutic effects in the treatment of Herpes Stromal Keratitis (HSK).IMPORTANCEOf the many problems associated with recurrent ocular infection, reducing virus reactivation should be a major goal of controlling ocular herpes simplex virus-1 (HSV-1) infection. In this study, we have shown that the absence of CD80 reduces HSV-1 reactivation, which marks the establishment of a previously undescribed mechanism underlying viral immune evasion that could be exploited to better manage HSV infection.
单纯疱疹病毒-1（HSV-1）感染是美国最常见的严重病毒性眼部感染之一，也是病毒性致盲的主要原因。已知 HSV-1 感染可诱导 T 细胞活化、增殖和分化，这些过程在病毒诱导的炎症病变发展中起着至关重要的作用，导致眼部疾病并引起慢性角膜损伤。CD80 是一种共刺激分子，在 T 细胞分化中起主导作用。以前通过控制细胞水平的炎症来限制病变严重程度的努力促使我们提出，CD80 敲除小鼠在重新激活后是否会表现出病毒复制减弱。通过评估 CD80 活性对原发性和潜伏性感染的影响，我们发现，在缺乏 CD80 的情况下，眼部的病毒复制和潜伏三叉神经节中的病毒再激活均显著减少。然而，潜伏感染的 CD80 小鼠的潜伏期与野生型（WT）对照小鼠没有显著差异。与 WT 小鼠相比，CD80 小鼠眼部的病毒复制减少与 CD11c 基因表达显著扩展相关。总之，我们的研究结果表明，抑制 CD80 可能在治疗疱疹性基质角膜炎（HSK）方面提供显著的有益治疗效果。重要性在与复发性眼部感染相关的许多问题中，减少病毒再激活应该是控制单纯疱疹病毒-1（HSV-1）眼部感染的主要目标。在这项研究中，我们已经表明 CD80 的缺失减少了 HSV-1 的再激活，这标志着一种以前未描述的病毒免疫逃避机制的建立，该机制可以被利用来更好地管理 HSV 感染。
