Antibody responses during hepatitis B viral infection.
Antibody responses during hepatitis B viral infection.
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DOI：
10.1371/journal.pcbi.1003730
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发表时间：
2014-07
影响因子：
4.3
通讯作者：
Perelson AS
中科院分区：
文献类型：
--
作者：
Ciupe SM;Ribeiro RM;Perelson AS
B型肝炎是一种感染肝细胞的DNA病毒，可引起急性和慢性疾病。据信，病毒和宿主因素都是决定感染是否被清除或成为慢性的原因。在这里，我们调查的保护机制，通过开发一个数学模型的抗体反应后，B型肝炎病毒（HBV）感染。我们将该模型拟合到急性感染期间确定的7名感染成人的数据，并确定病毒通过过量产生非感染性亚病毒颗粒逃避中和的能力，这些亚病毒颗粒表面具有HBs蛋白，但不含核衣壳蛋白和病毒核酸。我们发现，当（1）B型肝炎亚病毒颗粒的合成速度慢时，在高水平抗HBV抗体的情况下，可以实现病毒清除，就像在接种疫苗的个体中一样;（2）B型肝炎亚病毒颗粒合成率高但抗HBV抗体产生快，抗体亲和力高，或者在感染时预先存在的HBV特异性抗体水平很高，这可以通过接种疫苗来实现。我们进一步表明，当强细胞免疫应答控制早期感染时，可以在低平衡抗HBV抗体水平下实现病毒清除，如未接种疫苗的个体。B型肝炎疫苗在接种个体中诱导终身保护。然而，在没有接种疫苗的情况下，B型肝炎病毒可引起自限性和慢性疾病。我们研究抗B型肝炎抗体是否在病毒清除中发挥作用。我们开发了一个数学模型，该模型描述了感染性病毒和非感染性亚病毒颗粒（具有乙型肝炎B表面蛋白，但没有核酸）的抗体产生，并将该模型与患者数据进行了比较。我们预测，高水平的抗体，无论是预先存在的，如在接种疫苗的个人，或通过快速扩增，可以控制感染，并导致病毒清除。然而，当抗体水平与临床情况下观察到的抗体水平更相似时，需要细胞免疫应答来控制病毒，并且抗体仅在晚期阶段起作用以帮助病毒清除。
Hepatitis B is a DNA virus that infects liver cells and can cause both acute and chronic disease. It is believed that both viral and host factors are responsible for determining whether the infection is cleared or becomes chronic. Here we investigate the mechanism of protection by developing a mathematical model of the antibody response following hepatitis B virus (HBV) infection. We fitted the model to data from seven infected adults identified during acute infection and determined the ability of the virus to escape neutralization through overproduction of non-infectious subviral particles, which have HBs proteins on their surface, but do not contain nucleocapsid protein and viral nucleic acids. We showed that viral clearance can be achieved for high anti-HBV antibody levels, as in vaccinated individuals, when: (1) the rate of synthesis of hepatitis B subviral particles is slow; (2) the rate of synthesis of hepatitis B subviral particles is high but either anti-HBV antibody production is fast, the antibody affinity is high, or the levels of pre-existent HBV-specific antibody at the time of infection are high, as could be attained by vaccination. We further showed that viral clearance can be achieved for low equilibrium anti-HBV antibody levels, as in unvaccinated individuals, when a strong cellular immune response controls early infection. Hepatitis B vaccine induces life-long protection in vaccinated individuals. In the absence of vaccination, however, hepatitis B virus can cause both self-limiting and chronic disease. We investigate whether antibodies against hepatitis B play a role in virus clearance. We developed a mathematical model that describes the production of antibodies to both infectious virus and non-infectious subviral particles (with hepatitis B surface proteins, but no nucleic acids) and compared the model to patient data. We predict that high levels of antibodies, either pre-existing, as in vaccinated individuals, or through fast expansion, can control the infection and lead to viral clearance. However, when the antibody levels are more similar to those observed in a clinical context, cellular immune responses are needed to control the virus and antibodies act only in late stages to aid in viral clearance.
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影响因子：
2
作者：
Ciupe, Stanca M.;Ribeiro, Ruy M.;Perelson, Alan S.
通讯作者：
Perelson, Alan S.
影响因子：
2.2
作者：
ANHTUAN, N;NOVAK, E
通讯作者：
NOVAK, E
影响因子：
6
作者：
Chisari, FV
通讯作者：
Chisari, FV
DOI：
10.1073/pnas.94.13.6971
发表时间：
1997-06-24
影响因子：
11.1
作者：
Bonhoeffer, S;May, RM;Nowak, MA
通讯作者：
Nowak, MA
影响因子：
32.4
作者：
Guidotti, LG;Ishikawa, T;Chisari, FV
通讯作者：
Chisari, FV