Immunodominant epitopes mapped by synthetic peptides on the capsid protein of avian hepatitis E virus are non-protective
Immunodominant epitopes mapped by synthetic peptides on the capsid protein of avian hepatitis E virus are non-protective
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DOI：
10.1089/vim.2007.0082
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发表时间：
2008-03-01
期刊：
影响因子：
2.2
通讯作者：
Meng, X. J.
中科院分区：
文献类型：
--
作者：
Guo, Hailong;Zhou, E. M.;Meng, X. J.
禽戊型肝炎病毒（HEV）是最近在美国发现的一种感染鸡肝炎-脾肿大综合征的病毒。禽戊型肝炎病毒开放阅读框2（ORF 2）蛋白与人和猪戊型肝炎病毒ORF 2蛋白有交叉反应，并通过人工合成肽鉴定了禽戊型肝炎病毒ORF 2蛋白的免疫优势抗原表位。然而，这些表位是否对禽HEV感染具有保护性尚未研究。在这项研究中，鸡群免疫与钥孔血蓝蛋白（KLH）结合的肽和重组禽戊型肝炎病毒ORF 2抗原，然后与禽戊型肝炎病毒的攻击，以评估这些肽含有表位的保护能力。虽然禽戊型肝炎病毒ORF 2蛋白表现出完全的保护作用，对感染，病毒血症和粪便病毒脱落中发现的所有肽免疫鸡。采用纯化的抗肽IgY和抗鸡HEV ORF 2抗体，进行体外中和和体内监测试验，以进一步评价抗肽IgY的中和能力。结果表明，抗肽IgY均不能在体外中和禽戊型肝炎病毒，混合抗肽IgY和混合正常IgY接种的鸡均出现病毒血症、粪便排毒和血清转化。如预期的，用禽HEV和抗禽HEV ORF 2 IgY混合物接种的鸡未显示可检测的禽HEV感染。综上所述，本研究的结果表明，通过合成肽鉴定的禽HEV ORF 2蛋白上的免疫显性表位是非保护性的，这表明禽HEV ORF 2上的保护性中和表位可能不像人HEV那样是线性的。
Avian hepatitis E virus (avian HEV) was recently discovered in chickens with hepatitis-splenomegaly syndrome in the United States. The open reading frame 2 (ORF2) protein of avian HEV has been shown to cross-react with human and swine HEV ORF2 proteins, and immunodominant antigenic epitopes on avian HEV ORF2 protein were identified in the predicted antigenic domains by synthetic peptides. However, whether these epitopes are protective against avian HEV infection has not been investigated. In this study, groups of chickens were immunized with keyhole limpet hemocyanin (KLH)-conjugated peptides and recombinant avian HEV ORF2 antigen followed by challenge with avian HEV virus to assess the protective capacity of these peptides containing the epitopes. While avian HEV ORF2 protein showed complete protection against infection, viremia and fecal virus shedding were found in all peptide-immunized chickens. Using purified IgY from normal, anti-peptide, and anti-avian HEV ORF2 chicken sera, an in-vitro neutralization and in-vivo monitoring assay was performed to further evaluate the neutralizing ability of anti-peptide IgY. Results showed that none of the anti-peptide IgY can neutralize avian HEV in vitro, as viremia, fecal virus shedding, and seroconversion appeared similarly in chickens inoculated with avian HEV mixed with anti-peptide IgY and chickens inoculated with avian HEV mixed with normal IgY. As expected, chickens inoculated with the avian HEV and anti-avian HEV ORF2 IgY mixture did not show detectable avian HEV infection. Taken together, the results of this study demonstrated that immunodominant epitopes on avian HEV ORF2 protein identified by synthetic peptides are non-protective, suggesting protective neutralizing epitope on avian HEV ORF2 may not be linear as is human HEV.