Jaggi Ujjaldeep, Wang Shaohui, Mott Kevin R, Ghiasi Homayon
Center for Neurobiology and Vaccine Development, Department of Surgery, CSMC - SSB3, Los Angeles, California, United States of America.
PLoS Pathog. 2023 Sep 22;19(9):e1011693. doi: 10.1371/journal.ppat.1011693. eCollection 2023 Sep.
Previously we reported that the HSV-1 latency associated transcript (LAT) specifically upregulates the cellular herpesvirus entry mediator (HVEM) but no other known HSV-1 receptors. HSV-1 glycoprotein D (gD) binds to HVEM but the effect of this interaction on latency-reactivation is not known. We found that the levels of latent viral genomes were not affected by the absence of gD binding to HVEM. However, reactivation of latent virus in trigeminal ganglia explant cultures was blocked in the absence of gD binding to HVEM. Neither differential HSV-1 replication and spread in the eye nor levels of latency influenced reactivation. Despite similar levels of latency, reactivation in the absence of gD binding to HVEM correlated with reduced T cell exhaustion. Our results indicate that HVEM-gD signaling plays a significant role in HSV-1 reactivation but not in ocular virus replication or levels of latency. The results presented here identify gD binding to HVEM as an important target that influences reactivation and survival of ganglion resident T cells but not levels of latency. This concept may also apply to other herpesviruses that engages HVEM.
此前我们报道过，单纯疱疹病毒1型（HSV-1）潜伏相关转录本（LAT）特异性上调细胞疱疹病毒进入介质（HVEM），但不影响其他已知的HSV-1受体。HSV-1糖蛋白D（gD）与HVEM结合，但其对潜伏-再激活的影响尚不清楚。我们发现，gD与HVEM结合缺失并不影响潜伏病毒基因组的水平。然而，在三叉神经节外植体培养中，若gD与HVEM结合缺失，则潜伏病毒的再激活受阻。HSV-1在眼内的复制和扩散差异以及潜伏水平均不影响再激活。尽管潜伏水平相似，但gD与HVEM结合缺失时的再激活与T细胞耗竭减少相关。我们的结果表明，HVEM-gD信号传导在HSV-1再激活中起重要作用，但在眼内病毒复制或潜伏水平方面不起作用。本文结果表明，gD与HVEM结合是一个重要靶点，其影响神经节驻留T细胞的再激活和存活，但不影响潜伏水平。这一概念可能也适用于其他与HVEM相互作用的疱疹病毒。
