Center for Molecular Medicine and Infectious Diseases, Department of Biomedical Sciences and Pathobiology, College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA.
Virus Res. 2011 Jul;159(1):17-22. doi: 10.1016/j.virusres.2011.04.010. Epub 2011 Apr 22.
Hepatitis E virus (HEV) is an important human pathogen. At least four recognized and two putative genotypes of mammalian HEV have been reported: genotypes 1 and 2 are restricted to humans whereas genotypes 3 and 4 are zoonotic. The current experimental vaccines are all based on a single strain of HEV, even though multiple genotypes of HEV are co-circulating in some countries and thus an individual may be exposed to more than one genotype. Genotypes 3 and 4 swine HEV is widespread in pigs and known to infect humans. Therefore, it is important to know if prior infection with a genotype 3 swine HEV will confer protective immunity against subsequent exposure to genotypes 3 and 4 human and swine HEV. In this study, specific-pathogen-free pigs were divided into 4 groups of 6 each. Pigs in the three treatment groups were each inoculated with a genotype 3 swine HEV, and 12 weeks later, challenged with the same genotype 3 swine HEV, a genotype 3 human HEV, and a genotype 4 human HEV, respectively. The control group was inoculated and challenged with PBS buffer. Weekly sera from all pigs were tested for HEV RNA and IgG anti-HEV, and weekly fecal samples were also tested for HEV RNA. The pigs inoculated with swine HEV became infected as evidenced by fecal virus shedding and viremia, and the majority of pigs also developed IgG anti-HEV prior to challenge at 12 weeks post-inoculation. After challenge, viremia was not detected and only two pigs challenged with swine HEV had 1-week fecal virus shedding, suggesting that prior infection with a genotype 3 swine HEV prevented pigs from developing viremia and fecal virus shedding after challenges with homologous and heterologous genotypes 3 and 4 HEV. The results from this study have important implications for future development of an effective HEV vaccine.
戊型肝炎病毒（HEV）是一种重要的人类病原体。至少有四种已被确认和两种假定的哺乳动物 HEV 基因型：基因型 1 和 2仅限于人类，而基因型 3 和 4是动物源性的。目前的实验性疫苗均基于 HEV 的单一毒株，尽管在一些国家存在多种 HEV 基因型共同传播，因此个体可能会接触到不止一种基因型。基因型 3 和 4 猪 HEV 在猪中广泛传播，已知会感染人类。因此，了解先前感染基因型 3 猪 HEV 是否会对随后接触基因型 3 和 4 人类和猪 HEV 产生保护性免疫非常重要。在这项研究中，将无特定病原体猪分为 4 组，每组 6 只。三组治疗组的猪分别接种基因型 3 猪 HEV，12 周后，分别用相同的基因型 3 猪 HEV、基因型 3 人类 HEV 和基因型 4 人类 HEV 进行攻毒。对照组用 PBS 缓冲液接种和攻毒。每周从所有猪采集血清检测 HEV RNA 和 IgG 抗-HEV，每周还采集粪便样本检测 HEV RNA。接种猪 HEV 的猪出现了感染，表现为粪便病毒脱落和病毒血症，大多数猪在接种后 12 周攻毒前也产生了 IgG 抗-HEV。攻毒后未检测到病毒血症，仅 2 只攻毒猪出现 1 周粪便病毒脱落，表明先前感染基因型 3 猪 HEV 可防止猪在同源和异源基因型 3 和 4 HEV 攻毒后发生病毒血症和粪便病毒脱落。这项研究的结果对未来有效 HEV 疫苗的开发具有重要意义。
