Challenge pools of hepatitis C virus genotypes 1-6 prototype strains: replication fitness and pathogenicity in chimpanzees and human liver-chimeric mouse models.
Challenge pools of hepatitis C virus genotypes 1-6 prototype strains: replication fitness and pathogenicity in chimpanzees and human liver-chimeric mouse models.
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DOI：
10.1086/651579
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发表时间：
2010-05-01
期刊：
影响因子：
--
通讯作者：
Purcell RH
中科院分区：
文献类型：
--
作者：
Bukh J;Meuleman P;Tellier R;Engle RE;Feinstone SM;Eder G;Satterfield WC;Govindarajan S;Krawczynski K;Miller RH;Leroux-Roels G;Purcell RH
黑猩猩是研究丙型肝炎病毒（HCV）自然史的唯一动物模型。为了产生重要的HCV变异体的病毒储备，我们用基因型1-6的HCV毒株感染黑猩猩，并在其他动物中测定急性期血浆池的感染性滴度。第一代和第二代感染的病程相似，早期出现病毒血症，HCV RNA滴度>104.7 IU/mL，并发展为急性肝炎;慢性率为56%。挑战样本池的滴度为103-105黑猩猩感染剂量/mL。人肝嵌合体小鼠在接种基因型1-6的攻击病毒后发生高滴度感染。不同剂量的基因型1b库的接种研究表明，需要相对较高的病毒剂量才能持续感染嵌合小鼠。挑战池代表了HCV分子病毒学研究和致病机制、保护性免疫和疫苗体内效力研究的独特资源。
Chimpanzees represent the only animal model for studies of the natural history of hepatitis C virus (HCV). To generate virus stocks of important HCV variants, we infected chimpanzees with HCV strains of genotypes 1–6 and determined the infectivity titer of acute-phase plasma pools in additional animals. The courses of first- and second-passage infections were similar, with early appearance of viremia, HCV RNA titers of >104.7 IU/mL, and development of acute hepatitis; the chronicity rate was 56%. The challenge pools had titers of 103–105 chimpanzee infectious doses/mL. Human liver–chimeric mice developed high-titer infections after inoculation with the challenge viruses of genotypes 1–6. Inoculation studies with different doses of the genotype 1b pool suggested that a relatively high virus dose is required to consistently infect chimeric mice. The challenge pools represent a unique resource for studies of HCV molecular virology and for studies of pathogenesis, protective immunity, and vaccine efficacy in vivo.
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DOI：
10.1073/pnas.90.17.8234
发表时间：
1993-09-01
影响因子：
11.1
作者：
BUKH, J;PURCELL, RH;MILLER, RH
通讯作者：
MILLER, RH
影响因子：
5.4
作者：
Bassett, SE;Brasky, KM;Lanford, RE
通讯作者：
Lanford, RE
影响因子：
82.9
作者：
Law, Mansun;Maruyama, Toshiaki;Burton, Dennis R.
通讯作者：
Burton, Dennis R.
影响因子：
12.7
作者：
Engle, Ronald E.;Russell, Rodney S.;Bukh, Jens
通讯作者：
Bukh, Jens
影响因子：
13.5
作者：
Meuleman, Philip;Hesselgesser, Joseph;Leroux-Roels, Geert
通讯作者：
Leroux-Roels, Geert