Unique resistance of I/LnJ mice to a retrovirus is due to sustained interferon γ-dependent production of virus-neutralizing antibodies
Unique resistance of I/LnJ mice to a retrovirus is due to sustained interferon γ-dependent production of virus-neutralizing antibodies
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DOI：
10.1084/jem.20021499
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发表时间：
2003-01-20
影响因子：
15.3
通讯作者：
Golovkina, T
中科院分区：
文献类型：
--
作者：
Purdy, A;Case, L;Golovkina, T
免疫逃逸变异的选择损害了免疫系统维持有效抗病毒反应和控制逆转录病毒感染的能力。与其他逆转录病毒一样，小鼠乳腺肿瘤病毒（MMTV）不能被易感小鼠的免疫系统有效地消除。相比之下，mmtv感染的I/Lnj小鼠能够产生IgG2a病毒中和抗体，并在其一生中维持这种反应，并将抗体包裹的病毒粒子分泌到乳汁中，从而防止其后代感染。抗体是针对几种MMTV变体产生的，并与它们发生交叉反应。对MMTV感染的抗性是隐性的，依赖于干扰素(IFN)- γ的产生，因为靶向删除干扰素- γ基因的I/Lnj小鼠不能产生任何病毒中和抗体。这些发现揭示了一种新的抗逆转录病毒感染的机制，这种机制基于强大和持续的ifn - γ依赖性体液免疫反应。
Selection of immune escape variants impairs the ability of the immune system to sustain an efficient antiviral response and to control retroviral infections. Like other retroviruses, mouse mammary tumor virus (MMTV) is not efficiently eliminated by the immune system of susceptible mice. In contrast, MMTV-infected I/Lnj mice are capable of producing IgG2a virus-neutralizing antibodies, sustain this response throughout their life, and secrete antibody-coated virions into the milk, thereby preventing infection of their progeny. Antibodies were produced in response to several MMTV variants and were cross-reactive to them. Resistance to MMTV infection was recessive and was dependent on interferon (IFN)-gamma production, because I/Lnj mice with targeted deletion of the INF-gamma gene failed to produce any virus-neutralizing antibodies. These findings reveal a novel mechanism of resistance to retroviral infection that is based on a robust and sustained IFN-gamma-dependent humoral immune response.