title: Strong innate immune response and cell death in chicken splenocytes infected with genotype VIId Newcastle disease virus.
abstract: BACKGROUND
  Genotype VIId Newcastle disease virus (NDV) isolates induce more severe damage to lymphoid tissues, especially to the spleen, when compared to virulent viruses of other genotypes. However, the biological basis of the unusual pathological changes remains largely unknown.
  
  
  METHODS
  Virus replication, cytokine gene expression profile and cell death response in chicken splenocytes infected with two genotype VIId NDV strains (JS5/05 and JS3/05), genotype IX NDV strain F48E8 and genotype IV NDV strain Herts/33 were evaluated. Statistical significance of differences between experimental groups was determined using the Independent-Samples T test.
  
  
  RESULTS
  JS5/05 and JS3/05 caused hyperinduction of type I interferons (IFNs) (IFN-α and -β) during detection period compared to F48E8 and Herts/33. JS5/05 increased expression level of IFN-γ gene at 6 h post-inoculation (pi) and JS3/05 initiated sustained activation of IFN-γ within 24 h pi, whereas transcriptional levels of IFN-γ remained unchanged at any of the time points during infection of F48E8 and Herts/33. In addition, compared to F48E8 and Herts/33, JS3/05 and JS5/05 significantly increased the amount of free nucleosomal DNA in splenocytes at 6 and 24 h pi respectively. Annexin-V and Proidium iodid (PI) double staining of infected cells showed that cell death induced by JS3/05 and JS5/05 was characterized by marked necrosis compared to F48E8 and Herts/33 at 24 h pi. These results indicate that genotype VIId NDV strains JS3/05 and JS5/05 elicited stronger innate immune and cell death responses in chicken splenocytes than F48E8 and Herts/33. JS5/05 replicated at a significantly higher efficiency in splenocytes than F48E8 and Herts/33. Early excessive cell death induced by JS3/05 infection partially impaired virus replication.
  
  
  CONCLUSIONS
  Viral dysregulaiton of host response may be relevant to the severe pathological manifestation in the spleen following genotype VIId NDV infection.
authors.affiliation: Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, 12 East Wenhui Road, Yangzhou Jiangsu Province, 225009, China.
authors.forename: Zenglei
authors.initials: Z
authors.lastname: Hu
authors.forename: Jiao
authors.initials: J
authors.lastname: Hu
authors.forename: Shunlin
authors.initials: S
authors.lastname: Hu
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Liu
authors.forename: Xiaoquan
authors.initials: X
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.forename: Xiufan
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis; D016923:Cell Death; D002478:Cells, Cultured; D002645:Chickens; D005838:Genotype; D007370:Interferon Type I / Q000235:genetics / Q000276:immunology; D009521:Newcastle Disease / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology* / Q000821:virology; D009522:Newcastle disease virus / Q000145:classification / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D011201:Poultry Diseases / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology / Q000821:virology; D013154:Spleen / Q000166:cytology* / Q000276:immunology / Q000821:virology
chemical_list: D007370:Interferon Type I