The aging process is characterized by cellular functional decline and increased susceptibility to infections. Understanding the association between virus infection and aging is crucial for developing effective strategies against viral infections in older individuals. However, the relationship between Kaposi's sarcoma-associated herpesvirus (KSHV) infection, a cause of Kaposi's sarcoma prevalent among the elderly without HIV infection, and cellular senescence remains enigmatic. This study uncovers a fascinating link between cellular senescence and enhanced KSHV infectivity in human endothelial cells. Through a comprehensive proteomic analysis, we identified caveolin-1 and CD109 as novel host factors significantly upregulated in senescent cells that promote KSHV infection. Remarkably, CRISPR-Cas9-mediated knockout of these factors reduced KSHV binding and entry, leading to decreased viral infectivity. Furthermore, surface plasmon resonance analysis and confocal microscopy revealed a direct interaction between KSHV virions and CD109 on the cell surface during entry, with recombinant CD109 protein exhibiting an intriguing ability to inhibit infection by blocking virion binding. These findings uncover a previously unrecognized role of cellular senescence in enhancing KSHV infection through upregulation of specific host factors and provide novel insights into the complex interplay between aging and viral pathogenesis.

中文翻译：

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内皮细胞的衰老通过 CD109 介导的病毒进入增加了对卡波西肉瘤相关疱疹病毒感染的易感性。


衰老过程的特征是细胞功能下降和对感染的易感性增加。了解病毒感染与衰老之间的关联对于制定针对老年人病毒感染的有效策略至关重要。然而，卡波西肉瘤相关疱疹病毒 （KSHV） 感染（导致卡波西肉瘤在未感染 HIV 的老年人中普遍存在的原因）与细胞衰老之间的关系仍然是一个谜。这项研究揭示了人类内皮细胞中细胞衰老与增强的 KSHV 感染性之间的迷人联系。通过全面的蛋白质组学分析，我们确定 caveolin-1 和 CD109 是在促进 KSHV 感染的衰老细胞中显着上调的新型宿主因子。值得注意的是，CRISPR-Cas9 介导的这些因子敲除减少了 KSHV 的结合和进入，导致病毒感染性降低。此外，表面等离子体共振分析和共聚焦显微镜显示，在进入过程中，KSHV 病毒粒子与细胞表面的 CD109 之间存在直接相互作用，重组 CD109 蛋白表现出通过阻断病毒粒子结合来抑制感染的有趣能力。这些发现揭示了细胞衰老通过上调特定宿主因子在增强 KSHV 感染中以前未被认识的作用，并为衰老与病毒发病机制之间的复杂相互作用提供了新的见解。