健康鸡源自然减毒传染性喉气管炎病毒的基因组特征及疫苗潜力

文献信息

中文摘要

背景： 传染性喉气管炎（ILT）是由传染性喉气管炎病毒（ILTV）引起的一种鸡急性、高度接触性呼吸道疾病，持续给全球家禽业造成重大经济损失。目前的减毒活疫苗虽然有效，但存在残余毒力、毒力返强和建立潜伏感染的风险。迫切需要开发更安全、更有效的候选疫苗。方法：本研究在中国河南省常规诊断监测过程中，从临床健康蛋鸡中分离到一株ILTV毒株，命名为CH/HN/2022。该鸡群无ILT疫苗接种史，采样时无ILT临床症状。对CH/HN/2022的完整基因组进行了测序，其长度为152,218 bp，G+C含量为48%，预测有79个开放阅读框。结果：系统发育分析显示，CH/HN/2022与美国强毒株81658和USDA以及TCO疫苗株LT-IVAX（Clade II）聚为一簇，与81658株的核苷酸同一性为98.8%，但与先前报道的15株中国分离株的同一性仅为95.8-96.5%。值得注意的是，与中国强毒株相比，CH/HN/2022在UL区存在约3,340 bp缺失，在末端和内部重复区存在855 bp插入。与强毒株WG的比较分析发现，gD、gJ和ORF C蛋白存在显著氨基酸差异。CH/HN/2022可在LMH细胞中高效复制。对4周龄SPF鸡的致病性评估表明，经气管内接种的鸡中，CH/HN/2022未引起死亡，仅在10%的鸡中出现轻微、短暂的呼吸道症状，且在所测试条件下未检测到向接触鸡的传播。通过滴眼途径单剂接种CH/HN/2022可对强毒WG株的致死性攻击提供完全保护。结论：这些结果表明，CH/HN/2022是一株自然减毒的ILTV毒株，具有独特的基因组特征、减毒表型以及在所测试条件下有前景的保护效力，是开发减毒活疫苗的有希望的候选株。

英文摘要

Infectious laryngotracheitis (ILT) is an acute, highly contagious respiratory disease of chickens caused by infectious laryngotracheitis virus (ILTV), which continues to pose significant economic losses to the poultry industry worldwide. Current live attenuated vaccines, while effective, carry risks of residual virulence, reversion to pathogenicity, and latent infection establishment. There is an urgent need to develop safer and more effective vaccine candidates. In this study, an ILTV strain, designated CH/HN/2022, was isolated from clinically healthy layers during routine diagnostic monitoring in Henan Province, China. The flock had no history of ILT vaccination and showed no clinical signs of ILT at the time of sampling. The complete genome of CH/HN/2022 was sequenced, comprising 152,218 bp with 48% G+C content and 79 predicted open reading frames. Phylogenetic analysis revealed that CH/HN/2022 clustered with US virulent strains 81658 and USDA and TCO vaccine strain LT-IVAX (Clade II) and shared 98.8% nucleotide identity with strain 81658, but only 95.8-96.5% identity with 15 previously reported Chinese isolates. Notably, CH/HN/2022 possessed a ∼3,340 bp deletion in the UL region and an 855 bp insertion in the terminal and internal repeat regions compared to Chinese virulent strains. Comparative analysis with virulent strain WG identified significant amino acid differences in gD, gJ, and ORF C proteins. The CH/HN/2022 could efficiently replicate in LMH cells. Pathogenicity assessment in 4-week-old SPF chickens demonstrated that CH/HN/2022 induced no mortality and only mild, transient respiratory signs in 10% of birds inoculated via the intratracheal route, with no detectable transmission to contact birds under the conditions tested. Vaccination with a single dose of CH/HN/2022 via eye drop provided complete protection against lethal challenge with virulent WG strain. These findings indicate that CH/HN/2022 is a naturally attenuated ILTV strain with unique genomic features and an attenuated phenotype and promising protective efficacy under the conditions tested, representing a promising candidate for live attenuated vaccine development.