{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T05:56:33Z","timestamp":1778133393807,"version":"3.51.4"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012261","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T00:00:00Z","timestamp":1717718400000}}],"reference-count":43,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T00:00:00Z","timestamp":1716854400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["KA 3492\/14-1"],"award-info":[{"award-number":["KA 3492\/14-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["KA 3492\/9-1"],"award-info":[{"award-number":["KA 3492\/9-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ceva Animal Health","award":["FC9777-A1"],"award-info":[{"award-number":["FC9777-A1"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Marek\u2019s 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 <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. Additionally, we examined HVT infection of feather follicles. We generated an HVT mutant lacking both TMRs (v\u0394TMR) 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 <jats:italic>in vivo<\/jats:italic>, we infected one-day-old chickens with HVT or v\u0394TMR. v\u0394TMR 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.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012261","type":"journal-article","created":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T18:41:15Z","timestamp":1716921675000},"page":"e1012261","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Impact of viral telomeric repeat sequences on herpesvirus vector vaccine integration and persistence"],"prefix":"10.1371","volume":"20","author":[{"given":"Caroline","family":"Denesvre","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"You","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvie","family":"R\u00e9my","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tereza","family":"Vychodil","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katia","family":"Courvoisier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zolt\u00e1n","family":"Penzes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca 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Li","year":"2011","journal-title":"Vaccine"},{"issue":"2","key":"ppat.1012261.ref005","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1637\/9935-091511-Reg.1","article-title":"Advancement in vaccination against Newcastle disease: recombinant HVT NDV provides high clinical protection and reduces challenge virus shedding with the absence of vaccine reactions","volume":"56","author":"V Palya","year":"2012","journal-title":"Avian Dis"},{"issue":"1","key":"ppat.1012261.ref006","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1080\/03079457.2011.631983","article-title":"Protection induced by commercially available live-attenuated and recombinant viral vector vaccines against infectious laryngotracheitis virus in broiler chickens","volume":"41","author":"A Vagnozzi","year":"2012","journal-title":"Avian Pathol"},{"key":"ppat.1012261.ref007","first-page":"56","article-title":"Efficacy of a recombinant HVT-H5 vaccine against challenge with two genetically divergent Indonesian 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