The Size of the Viral Inoculum Contributes to the Outcome of Hepatitis B Virus Infection
The Size of the Viral Inoculum Contributes to the Outcome of Hepatitis B Virus Infection
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DOI：
10.1128/jvi.00867-09
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发表时间：
2009-10-01
影响因子：
5.4
通讯作者：
Chisari, Francis V.
中科院分区：
文献类型：
--
作者：
Asabe, Shinichi;Wieland, Stefan F.;Chisari, Francis V.
病毒剂量对感染结果的影响尚不清楚。在这项研究中，我们表明，对于乙型肝炎病毒（HBV），接种量的大小有助于病毒传播和免疫启动的动力学，然后决定感染的结果。成年黑猩猩被连续稀释的单克隆HBV接种物感染。出乎意料的是，尽管病毒动力学有很大的不同，高剂量接种（每只动物10（10）个基因组当量[GE]）和低剂量接种（每只动物10(0)个基因组当量）在对数扩散后都能检测到CD4 t细胞反应，允许100%的肝细胞感染，并且需要长时间的免疫病理才能发生清除。相比之下，中间(10（7)和10(4)GE）接种在可检测到的对数扩散之前启动t细胞反应，并在0.1%的肝细胞被感染之前以最小的免疫病理突然终止。令人惊讶的是，在所有肝细胞被感染后，10(1)GE的剂量引发了t细胞反应，并引起了严重免疫病理的长期或持续感染。最后，在接种通常快速控制的接种物之前，CD4 t细胞耗尽阻止了t细胞的启动，并引起了最小免疫病理的持续感染。这些结果表明，病毒传播动力学和CD4 t细胞启动之间的关系决定了HBV感染的结果。
The impact of virus dose on the outcome of infection is poorly understood. In this study we show that, for hepatitis B virus (HBV), the size of the inoculum contributes to the kinetics of viral spread and immunological priming, which then determine the outcome of infection. Adult chimpanzees were infected with a serially diluted monoclonal HBV inoculum. Unexpectedly, despite vastly different viral kinetics, both high-dose inocula (10(10) genome equivalents [GE] per animal) and low-dose inocula (10(0) GE per animal) primed the CD4 T-cell response after logarithmic spread was detectable, allowing infection of 100% of hepatocytes and requiring prolonged immunopathology before clearance occurred. In contrast, intermediate (10(7) and 10(4) GE) inocula primed the T-cell response before detectable logarithmic spread and were abruptly terminated with minimal immunopathology before 0.1% of hepatocytes were infected. Surprisingly, a dosage of 10(1) GE primed the T-cell response after all hepatocytes were infected and caused either prolonged or persistent infection with severe immunopathology. Finally, CD4 T-cell depletion before inoculation of a normally rapidly controlled inoculum precluded T-cell priming and caused persistent infection with minimal immunopathology. These results suggest that the relationship between the kinetics of viral spread and CD4 T-cell priming determines the outcome of HBV infection.