Yamaguchi S, Imada T, Kaji N, Mase M, Tsukamoto K, Tanimura N, Yuasa N
National Institute of Animal Health, 3-1-1 Kannondai, Tsukuba, Ibaraki 305-0856, Japan1.
J Gen Virol. 2001 May;82(Pt 5):1233-1238. doi: 10.1099/0022-1317-82-5-1233.
The molecular basis of pathogenicity of the chicken anaemia virus (CAV) needs to be clarified in order to develop a safe, live virus vaccine. In this study, several high- and low-pathogenic infectious DNA clones were obtained from field virus samples after 12 or 38 passages in MDCC-MSB1 cells. The high-pathogenic clones induced a low haematocrit, low weight gain and high mortality. Nucleotide sequence analyses identified one amino acid, at residue 394 of the VP1 capsid protein, as a major determinant of pathogenicity. To determine the role of this amino acid in pathogenicity, chimeric infectious DNA clones and point-mutated clones were used for chicken pathogenicity tests. These analyses clearly demonstrated that residue 394 of VP1 was crucial for the pathogenicity of CAV; all of the cloned viruses with glutamine at this position were highly pathogenic, whereas those with histidine had low pathogenicity. Low-pathogenic CAV, based on an infectious DNA clone, is a candidate for a genetically homogeneous and stable CAV live vaccine.
为了研发一种安全的鸡贫血病毒（CAV）活病毒疫苗，需要阐明其致病的分子基础。在本研究中，从MDCC-MSB1细胞中传代12次或38次后的野外病毒样本中获得了几个高致病性和低致病性的感染性DNA克隆。高致病性克隆导致红细胞压积降低、体重增加缓慢和高死亡率。核苷酸序列分析确定衣壳蛋白VP1第394位氨基酸是致病性的主要决定因素。为了确定该氨基酸在致病性中的作用，嵌合感染性DNA克隆和点突变克隆用于鸡致病性试验。这些分析清楚地表明，VP1的第394位残基对CAV的致病性至关重要；该位置为谷氨酰胺的所有克隆病毒均具有高致病性，而组氨酸的克隆病毒致病性较低。基于感染性DNA克隆的低致病性CAV是基因同质且稳定的CAV活疫苗的候选者。
