Intergenotypic chimeric hepatitis E viruses (HEVs) with the genotype 4 human HEV capsid gene in the backbone of genotype 3 swine HEV are infectious in pigs.

Intergenotypic chimeric hepatitis E viruses (HEVs) with the genotype 4 human HEV capsid gene in the backbone of genotype 3 swine HEV are infectious in pigs.
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DOI:
10.1016/j.virusres.2010.12.011
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发表时间:
2011-03
期刊:
影响因子:
5
通讯作者:
Meng, Xiang-Jin
Meng, Xiang-Jin
中科院分区:
医学3区
文献类型:
--
作者:
Feagins, Alicia R.;Cordoba, Laura;Sanford, Brent J.;Dryman, Barbara A.;Huang, Yao-Wei;LeRoith, Tanya;Emerson, Suzanne U.;Meng, Xiang-Jin

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基因1型和2型戊型肝炎病毒(HEV)仅感染人类,而基因3型和4型戊型肝炎病毒既感染人类也感染猪。为了研究人猪跨种感染HEV的机制,本研究构建了5种基因型间嵌合病毒,并在体外和猪体内检测了它们的传染性。我们证明,在基因3型猪HEV的脊梁中,含有ORF2衣壳基因的4型人HEV嵌合病毒单独或与邻近的5 ‘连接区(JR)和3 ’非编码区(NCR)结合,在Huh7细胞中具有复制能力,并在HepG2/C3A细胞和猪中具有传染性,从而支持基因3型和4型人HEV起源于猪的假设。然而,在基因1型人HEV的主干中含有基因3型或基因4型HEV的JR+ORF2+3 ' NCR的嵌合病毒未能感染猪,这表明其他基因组区域如5 ' NCR和ORF1也可能参与HEV跨种感染。本研究结果首次提供了基因3型猪HEV与基因4型人HEV衣壳基因互换性的实验证据,对了解HEV跨种感染机制具有重要意义。
Genotypes 1 and 2 hepatitis E virus (HEV) infect only humans whereas genotypes 3 and 4 HEV infect both humans and pigs. To evaluate the mechanism of cross-species HEV infection between humans and swine, in this study we constructed five intergenotypic chimeric viruses and tested for their infectivity in vitro and in pigs. We demonstrated that chimeric viruses containing the ORF2 capsid gene either alone or in combination with its adjacent 5′ junction region (JR) and 3′ noncoding region (NCR) from a genotype 4 human HEV in the backbone of a genotype 3 swine HEV are replication-competent in Huh7 cells and infectious in HepG2/C3A cells and in pigs, and thus supporting the hypothesis that genotypes 3 and 4 human HEV are of swine origin. However, chimeric viruses containing the JR+ORF2+3′ NCR of genotypes 3 or 4 HEV in the backbone of genotype 1 human HEV failed to infect pigs, suggesting that other genomic regions such as 5′ NCR and ORF1 may also be involved in HEV cross-species infection. The results from this study provide the first experimental evidence of the exchangeability of the capsid gene between genotype 3 swine HEV and genotype 4 human HEV, and have important implications for understanding the mechanism of HEV cross-species infection.
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