Determination and analysis of the complete genomic sequence of avian hepatitis E virus (avian HEV) and attempts to infect rhesus monkeys with avian HEV

Determination and analysis of the complete genomic sequence of avian hepatitis E virus (avian HEV) and attempts to infect rhesus monkeys with avian HEV
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DOI:
10.1099/vir.0.79841-0
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发表时间:
2004-06-01
影响因子:
3.8
通讯作者:
Meng, XJ
Meng, XJ
中科院分区:
医学3区
文献类型:
--
作者:
Huang, FF;Sun, ZF;Meng, XJ

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禽戊型肝炎病毒是最近从美国一只患有肝炎-脾肿大综合征的鸡身上发现的,在基因和抗原性上与人和猪的戊型肝炎病毒有亲缘关系。在这项研究中,基因组测序完成,并试图用禽流感病毒感染恒河猴。禽HEV基因组全长6654个碱基,比人和猪HEV基因组短约600个碱基。与人和猪HEV基因组相似,禽HEV基因组由一个短的5‘非编码区(NCR)、三个部分重叠的开放阅读框(ORF)和一个3’NCR组成。禽HEV与人和猪HEV全基因组核苷酸序列的同源性约为50%,ORF1的同源性为48%-51%,ORF2的同源性为46%-48%,ORF3的同源性为29%-34%。观察到显著的遗传变异,如缺失和插入,特别是在禽类HEV的ORF1中。然而,ORF1功能结构域中的解旋酶和甲基转移酶等基序在禽类HEV和哺乳类HEV中相对保守,支持禽HEV是HepeVirus属的结论。系统发育分析表明,禽HEV是有别于人和猪HEV的一个分支。猪戊型肝炎病毒感染非人类灵长类动物,可能还感染人类,因此可能是人畜共患病。通过对两只恒河猴接种禽流感病毒的实验,试图确定禽类HEV是否也会跨物种感染。在接种的猴子中没有观察到病毒感染的证据,因为没有血清转换、病毒血症、粪便病毒脱落或血清肝酶升高。这项研究的结果证实了禽类HEV与人和猪的HEV既有亲缘又有区别;然而,与猪HEV不同的是,禽类HEV可能不会传播给非人类灵长类动物。
Avian hepatitis E virus (avian HEV), recently identified from a chicken with hepatitis-splenomegaly syndrome in the United States, is genetically and antigenically related to human and swine HEVs. In this study, sequencing of the genome was completed and an attempt was made to infect rhesus monkeys with avian HEV. The full-length genome of avian HEV, excluding the poly(A) tail, is 6654 bp in length, which is about 600 bp shorter than that of human and swine HEVs. Similar to human and swine HEV genomes, the avian HEV genome consists of a short 5' non-coding region (NCR) followed by three partially overlapping open reading frames (ORFs) and a 3'NCR. Avian HEV shares about 50% nucleotide sequence identity over the complete genome, 48-51% identity in ORF1, 46-48% identity in ORF2 and only 29-34% identity in ORF3 with human and swine HEV strains. Significant genetic variations such as deletions and insertions, particularly in ORF1 of avian HEV, were observed. However, motifs in the putative functional domains of ORF1, such as the helicase and methyltransferase, were relatively conserved between avian HEV and mammalian HEVs, supporting the conclusion that avian HEV is a member of the genus Hepevirus. Phylogenetic analysis revealed that avian HEV represents a branch distinct from human and swine HEVs. Swine HEV infects non-human primates and possibly humans and thus may be zoonotic. An attempt was made to determine whether avian HEV also infects across species by experimentally inoculating two rhesus monkeys with avian HEV. Evidence of virus infection was not observed in the inoculated monkeys as there was no seroconversion, viraemia, faecal virus shedding or serum liver enzyme elevation. The results from this study confirmed that avian HEV is related to, but distinct from, human and swine HEVs; however, unlike swine HEV, avian HEV is probably not transmissible to non-human primates.