Analysis of hepatitis C virus-inoculated chimpanzees reveals unexpected clinical profiles

Analysis of hepatitis C virus-inoculated chimpanzees reveals unexpected clinical profiles
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DOI:
10.1128/jvi.72.4.2589-2599.1998
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发表时间:
1998-04-01
影响因子:
5.4
通讯作者:
Lanford, RE
Lanford, RE
中科院分区:
医学2区
文献类型:
--
作者:
Bassett, SE;Brasky, KM;Lanford, RE

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被引文献

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研究了黑猩猩队列中丙型肝炎病毒(HCV)感染的临床过程,以更好地表征这种有价值的动物模型的结果。一项横断面研究的结果显示,基于逆转录(RT-PCR)分析,HCV接种黑猩猩中病毒血症的比例很低(39%)。病毒血症和抗-HCV抗体的存在之间的相关性进行了观察。病毒血症的黑猩猩和清除病毒的黑猩猩之间的抗体模式是不同的。病毒血症的黑猩猩对NS 3、NS 4和NS 5的抗体反应性更高。由于出乎意料的低百分比的黑猩猩持续感染HCV,进行了一小组HCV感染黑猩猩的病毒学特征的纵向分析,以确定病毒清除和抗体损失的动力学。这项研究还表明,低百分比(33%)的HCV接种黑猩猩持续病毒血症。对6只HCV感染动物的连续出血分析显示了4种不同的临床特征。在接种后5个月内,在4只动物中观察到病毒清除,抗HCV抗体逐渐或快速丢失。在两只动物中观察到以持续性HCV RNA和抗HCV抗体为特征的慢性携带者特征。其中一只黑猩猩是RT-PCR阳性,抗体阴性5年,因此代表了沉默的携带者。如果外推到人群中,这些数据将意味着可能发生显著百分比的未识别的HCV感染,并且沉默携带者可能代表潜在的感染性献血者。
The clinical course of hepatitis C virus (HCV) infections in a chimpanzee cohort was examined to better characterize the outcome of this valuable animal model. Results of a cross-sectional study revealed that a low percentage (39%) of HCV-inoculated chimpanzees were viremic based on reverse transcription (RT-PCR) analysis. A correlation was observed between viremia and the presence of anti-HCV antibodies. The pattern of antibodies was dissimilar among viremic chimpanzees and chimpanzees that cleared the virus. Viremic chimpanzees had a higher prevalence of antibody reactivity to NS3, NS4, and NS5. Since an unexpectedly low percentage of chimpanzees were persistently infected with HCV, a longitudinal analysis of the virological profile of a small panel of HCV-infected chimpanzees was performed to determine the kinetics of viral clearance and loss of antibody. This study also revealed that a low percentage (33%) of HCV-inoculated chimpanzees were persistently viremic. Analysis of serial bleeds from six HCV-infected animals revealed four different clinical profiles. Viral clearance with either gradual or rapid loss of anti-HCV antibody was observed in four animals within 5 months postinoculation. A chronic-carrier profile characterized by persistent HCV RNA and anti-HCV antibody was observed in two animals. One of these chimpanzees was RT-PCR positive, antibody negative for 5 years and thus represented a silent carrier. If extrapolated to the human population, these data would imply that a significant percentage of unrecognized HCV infections may occur and that silent carriers may represent potentially infectious blood donors.