Prolonged fecal shedding of hepatitis e virus (HEV) during sporadic acute hepatitis E: Evaluation of infectivity of HEV in fecal specimens in a cell culture system

Prolonged fecal shedding of hepatitis e virus (HEV) during sporadic acute hepatitis E: Evaluation of infectivity of HEV in fecal specimens in a cell culture system
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DOI:
10.1128/jcm.01086-07
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发表时间:
2007-11-01
影响因子:
9.4
通讯作者:
Okamoto, Hiroaki
Okamoto, Hiroaki
中科院分区:
医学2区
文献类型:
--
作者:
Takahashi, Masaharu;Tanaka, Toshinori;Okamoto, Hiroaki

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为探讨急性戊型肝炎患者粪便中戊型肝炎病毒(HEV)的排泄时间和病毒载量的变化,对11例散发性急性戊型肝炎患者的定期血清和粪便标本进行HEV RNA定量检测,11例患者入院时血清均可检测到HEV RNA,最高病毒载量为1.9×10(3)~1.7×10(7)拷贝/ml,HEV病毒血症持续至发病后第17~48天,平均28.3天。即使在第10至29天(平均17.6天)的初次检查中,11名患者中有10名患者粪便上清液中的HEV载量低于5.7×10(4)拷贝/毫升,而其余患者(患者1)的粪便上清液HEV载量在第22天显著高于2.0×10(7)拷贝/毫升。此外,虽然患者2至11的粪便上清液中的HEV RNA持续阳性,直到第14至33天(平均22.4天),但患者1的粪便上清液中的HEV RNA即使在第121天仍可检测到。患者1的粪便标本在第22、24、26、28和30天,而不是121天,在PLC/PRF/5细胞中高效生长,在接种后50天达到最高滴度,最高可达107拷贝/毫升。从患者1中恢复的HEV基因组有29个独特的核苷酸,这是在报道的25株相同基因的HEV分离株中未见的全基因组,在ORF1蛋白中有6个氨基酸替换。
To investigate the duration of fecal shedding and changing loads of hepatitis E virus (HEV) in feces and serum from patients with acute HEV infection, HEV RNA was quantitated in periodic serum and fecal specimens obtained from 11 patients with sporadic acute hepatitis E. All 11 patients had detectable HEV RNA in serum at admission, with the highest viral load being 1.9 x 10(3) to 1.7 x 10(7) copies/ml, and HEV viremia lasted until days 17 to 48 (mean, 28.3) after the onset of hepatitis. Even at the initial examination on days 10 to 29 (mean, 17.6), the HEV load in fecal supernatant was less than 5.7 X 10(4) copies/ml for 10 of the 11 patients, while for the remaining patient (patient 1) it was markedly high, 2.0 X 10(7) copies/ml on day 22. In addition, although HEV RNA in fecal supernatant continued to be positive until days 14 to 33 (mean, 22.4) for patients 2 to 11, that for patient I was detectable even on day 121. HEVs in fecal specimens obtained on days 22, 24, 26, 28, and 30, but not day 121, from patient 1 grew efficiently in PLC/PRF/5 cells, reaching the highest titer Of Up to 107 copies/ml in culture medium on day 50 postinoculation. The HEV genome recovered from patient 1 had 29 unique nucleotides that were not seen in any of the 25 reported HEV isolates of the same genotype over the entire genome, with six amino acid substitutions in the ORF1 protein.