Ni Jie, Deng Jing, Chen Qing, Liao Tianxing, Hu Jiao, Chen Yu, Hu Shunlin, Hu Zenglei, Liu Xiufan
Key Laboratory of Animal Infectious Diseases, School of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.
Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou 225009, China.
Animals (Basel). 2023 Jul 7;13(13):2239. doi: 10.3390/ani13132239.
Long-term evolution of Newcastle disease virus (NDV) results in substantial alteration in viral pathogenesis. NDVs of genotype VII, a late genotype, show marked tropism to lymphoid tissues, especially to macrophages in chickens. However, the role of macrophages in the pathogenesis of genotype VII NDV is still unclear. Herein, NDV infectivity in macrophages and the role of macrophages in the pathogenesis of genotype VII NDV in chickens were investigated. We reported that NDV strains of genotype VII (JS5/05) and IV (Herts/33) can replicate in the adherent (predominantly macrophages) and non-adherent cells (predominantly lymphocytes) derived from chicken peripheral blood mononuclear cells (PBMCs), and significantly higher virus gene copy was detected in the adherent cells. In addition, JS5/05 had significantly higher infectivity in PBMC-derived adherent cells than Herts/33, correlating with its enhanced tropism to macrophages in the spleen of chickens. Interestingly, the depletion of 68% of macrophages exerted no significant impact on clinical signs, mortality and the systematic replication of JS5/05 in chickens, which may be associated with the contribution of non-depleted macrophages and other virus-supportive cells to virus replication. Macrophage depletion resulted in a marked exacerbation of tissue damage and apoptosis in the spleen caused by JS5/05. These findings indicated that macrophages play a critical role in alleviating tissue damage caused by genotype VII NDV in chickens. Our results unveiled new roles of macrophages in NDV pathogenesis in chickens.
新城疫病毒（NDV）的长期进化导致病毒致病机制发生重大改变。VII型新城疫病毒是一种较新的基因型，对淋巴组织表现出明显的嗜性，尤其是对鸡体内的巨噬细胞。然而，巨噬细胞在VII型新城疫病毒致病机制中的作用仍不清楚。在此，我们研究了巨噬细胞中新城疫病毒的感染性以及巨噬细胞在鸡体内VII型新城疫病毒致病机制中的作用。我们发现，VII型（JS5/05）和IV型（Herts/33）新城疫病毒毒株能够在源自鸡外周血单个核细胞（PBMC）的贴壁细胞（主要是巨噬细胞）和非贴壁细胞（主要是淋巴细胞）中复制，并且在贴壁细胞中检测到显著更高的病毒基因拷贝数。此外，JS5/05在PBMC来源的贴壁细胞中的感染性显著高于Herts/33，这与其对鸡脾脏巨噬细胞的嗜性增强相关。有趣的是，去除68%的巨噬细胞对鸡的临床症状、死亡率以及JS5/05在鸡体内的全身复制没有显著影响，这可能与未被去除的巨噬细胞和其他支持病毒复制的细胞对病毒复制的贡献有关。巨噬细胞耗竭导致JS5/05引起的脾脏组织损伤和细胞凋亡明显加剧。这些发现表明，巨噬细胞在减轻鸡体内VII型新城疫病毒引起的组织损伤中起关键作用。我们的结果揭示了巨噬细胞在鸡新城疫病毒致病机制中的新作用。
