Repeated Exposure to Trace Amounts of Woodchuck Hepadnavirus Induces Molecularly Evident Infection and Virus-Specific T Cell Response in the Absence of Serological Infection Markers and Hepatitis
Repeated Exposure to Trace Amounts of Woodchuck Hepadnavirus Induces Molecularly Evident Infection and Virus-Specific T Cell Response in the Absence of Serological Infection Markers and Hepatitis
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DOI：
10.1128/jvi.01363-12
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发表时间：
2013-01-01
影响因子：
5.4
通讯作者：
Michalak, Tomasz I.
中科院分区：
文献类型：
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作者：
Gujar, Shashi A.;Mulrooney-Cousins, Patricia M.;Michalak, Tomasz I.
暴露于多个小剂量的B型肝炎病毒（HBV）是一种常见的高危人群，包括感染者的近亲，初级保健人员，静脉注射吸毒者。目前还不确定这种反复接触是否会导致无免疫保护的个体发生与肝炎同时发生的有症状的感染。在这项研究中，我们评估了多次暴露于小的，肝脏非致病性数量的传染性嗜肝DNA病毒的B型肝炎土拨鼠模型的后果。首次感染病毒的动物每周静脉注射6次110 DNA酶消化保护的土拨鼠肝炎病毒（WHV）病毒粒子，7.5个月后再次注射6次每周110病毒粒子，然后用1.1 x 10（6）相同接种物的肝脏致病剂量病毒粒子进行攻击或不攻击。数据显示，两轮这样的重复接触没有导致血清学上明显的感染或肝炎。然而，在缺乏抗病毒抗体反应的情况下，建立了低水平WHV DNA阳性感染，并伴有WHV特异性T细胞反应。病毒特异性和丝裂原诱导的（广义）T细胞反应的动力学和无法诱导免疫保护对抗挑战与一个大的，肝脏致病性的病毒剂量是密切可比的隐性感染开始由一个单一的肝脏非致病性剂量的WHV先前报道。因此，重复暴露于少量嗜肝DNA病毒诱导分子上明显但血清学上沉默的感染，其不以肝炎或产生免疫保护而达到高潮。这一发现意味着在没有感染血清学标志物的情况下，HBV特异性T细胞反应可能反映了正在进行的隐性感染。
Exposure to multiple small doses of hepatitis B virus (HBV) is a frequent occurrence in high-risk groups, including close relatives of infected individuals, primary care givers, and intravenous drug users. It remains uncertain whether such repeated contact may culminate in a symptomatic infection coinciding with hepatitis in individuals not immunoprotected. In this study, we evaluated consequences of multiple exposures to small, liver-nonpathogenic amounts of infectious hepadnavirus in the woodchuck model of hepatitis B. Virus-naive animals were intravenously injected with 6 weekly doses of 110 DNase digestion-protected virions of woodchuck hepatitis virus (WHV), injected again with 6 weekly 110-virion doses after 7.5 months, and then challenged or not with a liver-pathogenic dose of 1.1 x 10(6) virions of the same inoculum. The data revealed that two rounds of such repeated exposure did not result in serologically evident infection or hepatitis. However, a low-level WHV DNA-positive infection accompanied by a WHV-specific T cell response in the absence of antiviral antibody reactivity was established. The kinetics of the virus-specific and mitogen-induced (generalized) T cell responses and the inability to induce immunoprotection against challenge with a large, liver-pathogenic virus dose were closely comparable to those previously reported for occult infection initiated by a single liver-nonpathogenic dose of WHV. Thus, repeated exposures to small quantities of hepadnavirus induce molecularly evident but serologically silent infection that does not culminate in hepatitis or generate immune protection. The findings imply that the HBV-specific T cell response encountered in the absence of serological markers of infection likely reflects ongoing occult infection.