Avian Immunosuppressive Diseases Division, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, Harbin, China.
Jiangsu Co-innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonoses, Yangzhou University, Yangzhou, China.
Transbound Emerg Dis. 2022 Sep;69(5):e1702-e1709. doi: 10.1111/tbed.14506. Epub 2022 Mar 22.
Marek's disease virus (MDV), an oncogenic virus belonging to the subfamily Alphaherpesvirinae, causes Marek's disease (MD). Vaccines can control MD but cannot block the viral infection; they are considered imperfect vaccines, which carry the risk of recombination. In this study, six natural recombinant MDV strains were isolated from infected chickens in commercial flocks in China. We sequenced and analysed the genetic characteristics of the isolates (HC/0803, CH/10, SY/1219, DH/1307, DH/1504 and Hrb/1504). We found that the six strains resulted from recombination between the vaccine CVI988/Rispens (CVI988) strain skeleton and the virulence strain's partial unique short region. Additionally, a pathogenicity study was performed on recombinant strains (HC/0803 and DH/1307) and reference strains (CVI988 and LHC2) to evaluate their virulence. LHC2 induced 84.6% mortality in infected chickens; however, no mortality was recorded in chickens inoculated with HC/0803, DH/1307 or CVI988. However, HC/0803 and DH/1307 induced a notable spleen enlargement, and mild thymus and bursa atrophy at 11-17 days post-challenge (dpc). The viral genome load in the HC/0803- and DH/1307-challenged chickens peaked at approximately 10 viral copies per million host cells at 17 dpc and was similar to that in LHC2-challenged chickens, but significantly higher than that of CVI988-challenged chickens. In summary, HC/0803 and DH/1307 displayed mild virulence with temporal damage to the immune organs of chicken and a higher reproduction capability than the vaccine strain CVI988. Our study provides direct evidence of the emergence of recombinant MDV strains between vaccine and virulence strains in nature. The emergence of natural recombinant strains suggests that live vaccines can act as genetic donors for genomic recombination, and recombination may be a safety concern when administering live vaccines. These findings demonstrate that recombination promotes genetic diversity and increases the complexity of disease diagnosis, prevention and control.
马立克氏病病毒（MDV）是一种致瘤性病毒，属于α疱疹病毒亚科，可引起马立克氏病（MD）。疫苗可以控制 MD，但不能阻止病毒感染；它们被认为是不完美的疫苗，存在重组的风险。在本研究中，从中国商业鸡群中感染的鸡中分离出六株天然重组 MDV 株。我们对分离株（HC/0803、CH/10、SY/1219、DH/1307、DH/1504 和 Hrb/1504）的遗传特征进行了测序和分析。我们发现，这六株病毒是由疫苗 CVI988/Rispens（CVI988）株骨架与毒力株部分独特短区之间的重组产生的。此外，对重组株（HC/0803 和 DH/1307）和参考株（CVI988 和 LHC2）进行了致病性研究，以评估其毒力。LHC2 感染的鸡死亡率为 84.6%；然而，接种 HC/0803、DH/1307 或 CVI988 的鸡没有死亡。然而，HC/0803 和 DH/1307 在攻毒后 11-17 天引起明显的脾脏肿大，轻度胸腺和法氏囊萎缩。HC/0803 和 DH/1307 攻毒鸡的病毒基因组载量在 17 dpc 时约为每百万宿主细胞 10 个病毒拷贝，与 LHC2 攻毒鸡相似，但显著高于 CVI988 攻毒鸡。总之，HC/0803 和 DH/1307 表现出轻度毒力，会暂时损害鸡的免疫器官，并且繁殖能力高于疫苗株 CVI988。本研究提供了自然发生的疫苗株和毒力株之间出现重组 MDV 株的直接证据。自然重组株的出现表明，活疫苗可以作为基因组重组的遗传供体，而重组在使用活疫苗时可能是一个安全隐患。这些发现表明，重组促进了遗传多样性，增加了疾病诊断、预防和控制的复杂性。
