商业 SB-1 疫苗中的端粒重复序列促进病毒整合并有助于提高疫苗功效。
Telomeric repeats in the commercial SB-1 vaccine facilitate viral integration and contribute to vaccine efficacy.
发表日期:2024 Aug 21
作者:
Yu You, Ahmed M Kheimar, Tereza Vychodil, Lisa Kossak, Mohammad A Sabsabi, Andelé M Conradie, Sanjay M Reddy, Luca D Bertzbach, Benedikt B Kaufer
来源:
npj Vaccines
摘要:
马立克氏病病毒(MDV)将其基因组整合到宿主染色体的端粒中,引起鸡致命的淋巴瘤。病毒基因组末端的端粒重复序列 (TMR) 促进了这种整合,对于 MDV 诱导的淋巴瘤发生至关重要。 SB-1 疫苗病毒通常用于抗 MDV 的商业二价疫苗,并且其末端也含有 TMR。在这里,我们证明 SB-1 有效地将其基因组整合到潜伏感染 T 细胞的染色体中。从SB-1基因组中删除TMR并不会影响病毒复制,但会严重损害潜伏感染T细胞和鸡中的病毒整合和基因组维持。引人注目的是,潜在 SB-1 整合和维持的减少显着损害了疫苗保护。总而言之,我们的数据显示 TMR 促进 SB-1 整合,并且潜伏病毒基因组的整合和/或维护对于疫苗保护至关重要。© 2024。作者。
Marek's disease virus (MDV) integrates its genome into the telomeres of host chromosomes and causes fatal lymphomas in chickens. This integration is facilitated by telomeric repeat sequences (TMRs) at the ends of the viral genome, and is crucial for MDV-induced lymphomagenesis. The SB-1 vaccine virus is commonly used in commercial bivalent vaccines against MDV and also contains TMRs at its ends. Here, we demonstrate that SB-1 efficiently integrates its genome into the chromosomes of latently infected T cells. Deletion of the TMRs from the SB-1 genome did not affect virus replication, but severely impaired virus integration and genome maintenance in latently infected T cells and in chickens. Strikingly, the reduced integration and maintenance of latent SB-1 significantly impaired vaccine protection. Taken together, our data revealed that the TMRs facilitate SB-1 integration and that integration and/or maintenance of the latent viral genome is critical for vaccine protection.© 2024. The Author(s).