Hishikawa Sohta, Sunden Yuji, Imamura Aoi, Nishibayashi Junta, Hidaka Chiharu, Ito Hiroshi, Ito Toshihiro, Morita Takehito
Joint Graduate School of Veterinary Sciences, Tottori University, Tottori, Japan.
Joint Department of Veterinary Medicine, Faculty of Agriculture, Tottori University, Tottori, Japan.
J Vet Med Sci. 2025 May 1;87(5):481-489. doi: 10.1292/jvms.25-0002. Epub 2025 Mar 19.
Although velogenic Newcastle disease viruses (NDVs) generally show low pathogenicity in waterfowl such as ducks, lethal infection by NDVs has been reported sporadically. A previous study revealed that a serially-passaged NDV isolate showed increased virulence in ducks, and that the viral proteins harbored a total of 11 amino acid substitutions. Among them, the fusion protein (F), matrix protein (M), and hemagglutinin-neuraminidase (HN) were suspected to be involved in enhanced virulence. The present study aimed to clarify the association between genetic mutations in NDVs and pathogenicity in ducks by comparing histopathological findings in ducks inoculated with three recombinant (r) NDVs: rM44 (Q44R substitution in M), rF142 (I142M substitution in F), and rM+F+HN (Q44R, N123D, and D342N substitutions in M; I142M and E304K substitutions in F; and G538R substitution in HN; three viral proteins compatible with amino acid sequences from passaged NDV). Seven-day-old ducks were intranasally inoculated with rM44, rF142, or rM+F+HN. Gross and histopathological lesions in the heart, thymus, brain, and pancreas were more severe in ducks inoculated with rM+F+HN than in ducks inoculated with rM44 or rF142. In particular, myocarditis associated with NDV antigens and mixed inflammatory cells was prominent in rM+F+HN-inoculated ducks. Therefore, the increased virulence of NDV in ducks is not due to a single amino acid substitution in one protein, but rather to the synergistic effects of multiple mutations in three viral proteins.
虽然速发型新城疫病毒(NDV)通常在鸭等水禽中表现出低致病性,但NDV致死性感染的情况也有零星报道。先前的一项研究表明,一株连续传代的NDV分离株在鸭中的毒力增强,且该病毒蛋白共有11个氨基酸替换。其中,融合蛋白(F)、基质蛋白(M)和血凝素神经氨酸酶(HN)被怀疑与毒力增强有关。本研究旨在通过比较接种三种重组(r)NDV的鸭的组织病理学结果,阐明NDV基因突变与鸭致病性之间的关联:rM44(M蛋白中的Q44R替换)、rF142(F蛋白中的I142M替换)和rM+F+HN(M蛋白中的Q44R、N123D和D342N替换;F蛋白中的I142M和E304K替换;HN蛋白中的G538R替换;三种病毒蛋白与传代NDV的氨基酸序列一致)。7日龄鸭经鼻内接种rM44、rF142或rM+F+HN。接种rM+F+HN 的鸭心脏、胸腺、脑和胰腺的大体病变和组织病理学病变比接种rM44或rF142的鸭更严重。特别是,接种rM+F+HN的鸭中,与NDV抗原和混合炎性细胞相关的心肌炎很突出。因此,NDV在鸭中毒力增强并非由于一种蛋白中的单个氨基酸替换,而是由于三种病毒蛋白中多个突变的协同作用。