單純疱疹病毒感染角膜並進行複製時可引發血管新生及慢性發炎反應，進而造成臨床上最常導致視覺障礙的失明性角膜炎。由於病毒須仰賴宿主細胞供給資源以完成病毒本身的複製，因此宿主細胞因子可能參與病毒感染所誘發的疾病；然而其中參與的細胞因子種類，以及細胞因子在致病機轉中的可能作用機制仍不十分清楚。在我們的研究中發現單純疱疹病毒感染可以增加細胞轉錄因子Egr-1在小鼠眼角膜的表現。這些增加的Egr-1蛋白會促進病毒的複製與血管新生因子的表現，進而造成角膜的組織病變與血管新生。此外我們也發現不管是先天缺乏Egr-1蛋白的Egr-1基因缺陷鼠，或是使用Egr-1-specific DNAzyme抑制野生型小鼠角膜的Egr-1蛋白表現時，這些缺少Egr-1表現的小鼠，在被病毒感染後，其角膜組織的病變程度有顯著降低，同時組織中的病毒量與促血管新生因子的表現量都有顯著減少。我們結果顯示內生性的Egr-1蛋白會惡化疱疹病毒引起的失明性角膜炎，而抑制Egr-1蛋白的表現，則可以改善單純疱疹病毒感染所造成的失明性角膜炎。
單純疱疹病毒除了在周邊組織造成病變之外，也因為具有侵犯神經組織，並建立終生潛伏感染的能力，而成為人類健康的一大威脅。疱疹病毒性腦炎是單純疱疹病毒感染中樞神經系統所引發的致命疾病，但是目前為止疱疹病毒性腦炎的致病機制還不清楚。在本篇研究中我們發現，乙型類澱粉蛋白基因轉殖鼠在被單純疱疹病毒感染後，其死亡率有明顯的增加，同時也可在腦部偵測到大量的病毒存在。基因轉殖鼠腦部大量的病毒，可能是因為乙型類澱粉蛋白與病毒顆粒作用，增加病毒附著於細胞表面的數目，進而促進病毒的感染。我們的研究結果不僅發現乙型類澱粉蛋白可以幫助單純疱疹病毒感染細胞，同時也促進我們對疱疹病毒性腦炎致病機轉的認識。

Herpes simplex virus type 1 replication initiates angiogenesis and inflammation in the cornea. This can result in herpetic stromal keratitis (HSK), which is a leading cause of infection-induced corneal blindness. Host cellular factors mediate the progression of HSK, but little is known about these cellular factors and their mechanisms of action. We show here that the expression of the cellular transcription factor early growth response 1 (Egr-1) in HSV-1-infected mouse corneas was enhanced. Enhanced Egr-1 expression aggravated HSK by increasing viral replication and subsequent neovascularization with high levels of potent angiogenic factors, fibroblast growth factor 2 and vascular endothelial growth factor. Furthermore, Egr-1 deficiency due to a targeted disruption of the gene or knockdown of Egr-1 expression topically using a DNA-based enzyme significantly reduced HSK by decreasing both viral replication and the angiogenic response. The present study provides the first evidence that endogenous Egr-1 aggravates HSK and that blocking Egr-1 reduces corneal damage.
HSV-1 with its ability to invade neurons and establish life-long latent infection in infected hosts becomes a threat to our health. The most devastating disease caused by HSV-1 infection is herpes simplex encephalitis, although the pathogenesis remains unclear. We show here that transgenic mice with increased β-amyloid (Aβ) expression in the brain were susceptible to HSV-1-induced lethality and contained high viral loads in the brain. The increased viral loads were resulted from Aβ-mediated enhancement on virus binding to host cells through the interaction of Aβ and virus. Our present study indicates that Aβ acts as an entry enhancer of HSV-1 infection and also enhances our understanding of HSV-1-induced encephalitis.

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