马立克氏病病毒 (MDV) 疫苗是第一种预防癌症的疫苗。无毒力的火鸡疱疹病毒 (HVT) 被广泛使用，保护了数十亿只鸡免受致命的 MDV 感染。它也是最常见的疫苗载体之一，可提供针对多种病原体的保护。 HVT 在 T 细胞中建立潜伏期，使疫苗病毒能够在宿主体内终生存在。有趣的是，HVT 基因组的两端都含有端粒重复阵列 (TMR)；然而，它们在 HVT 生命周期中的作用仍然难以捉摸。我们之前已经表明，MDV 基因组中类似的 TMR 有助于其整合到宿主端粒中，从而确保病毒基因组在潜伏期和肿瘤发生期间的有效维护。在这项研究中，我们研究了 TMR 在体外和体内 HVT 基因组整合、潜伏期和重新激活中的作用。此外，我们还检查了羽毛毛囊的 HVT 感染。我们生成了一种缺乏两种 TMR (vΔTMR) 的 HVT 突变体，可以在细胞培养物中有效复制。我们可以证明野生型 HVT 整合在 T 细胞中含有端粒的染色体末端，而在没有 TMR 的情况下整合会受到严重损害。为了评估 TMR 在体内的作用，我们用 HVT 或 vΔTMR 感染一天大的鸡。血液中的 vΔTMR 负载显着减少，几乎没有任何病毒被输送到病毒通常脱落的羽毛毛囊上皮。引人注目的是，在没有 TMR 的情况下，病毒在脾脏中的潜伏期和重新激活受到严重损害，这表明 TMR 对于 HVT 潜伏期和重新激活的建立至关重要。我们的研究结果表明，TMR 有助于 HVT 基因组整合到宿主染色体中，从而确保病毒在宿主中有效持续存在、重新激活以及将病毒运输到皮肤。版权所有：© 2024 Denesvre 等人。这是一篇根据知识共享署名许可条款分发的开放获取文章，允许在任何媒体上不受限制地使用、分发和复制，前提是注明原始作者和来源。

Marek's disease virus (MDV) vaccines were the first vaccines that protected against cancer. The avirulent turkey herpesvirus (HVT) was widely employed and protected billions of chickens from a deadly MDV infection. It is also among the most common vaccine vectors providing protection against a plethora of pathogens. HVT establishes latency in T-cells, allowing the vaccine virus to persist in the host for life. Intriguingly, the HVT genome contains telomeric repeat arrays (TMRs) at both ends; however, their role in the HVT life cycle remains elusive. We have previously shown that similar TMRs in the MDV genome facilitate its integration into host telomeres, which ensures efficient maintenance of the virus genome during latency and tumorigenesis. In this study, we investigated the role of the TMRs in HVT genome integration, latency, and reactivation in vitro and in vivo. Additionally, we examined HVT infection of feather follicles. We generated an HVT mutant lacking both TMRs (vΔTMR) that efficiently replicated in cell culture. We could demonstrate that wild type HVT integrates at the ends of chromosomes containing the telomeres in T-cells, while integration was severely impaired in the absence of the TMRs. To assess the role of TMRs in vivo, we infected one-day-old chickens with HVT or vΔTMR. vΔTMR loads were significantly reduced in the blood and hardly any virus was transported to the feather follicle epithelium where the virus is commonly shed. Strikingly, latency in the spleen and reactivation of the virus were severely impaired in the absence of the TMRs, indicating that the TMRs are crucial for the establishment of latency and reactivation of HVT. Our findings revealed that the TMRs facilitate integration of the HVT genome into host chromosomes, which ensures efficient persistence in the host, reactivation, and transport of the virus to the skin.Copyright: © 2024 Denesvre et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.