Impairment of CD4(+) T cell responses during chronic virus infection prevents neutralizing antibody responses against virus escape mutants.
Impairment of CD4(+) T cell responses during chronic virus infection prevents neutralizing antibody responses against virus escape mutants.
复制标题
慢性病毒感染期间CD4（+）T细胞反应的损害可防止对病毒逃生突变体的中和抗体反应。
DOI：
10.1084/jem.193.3.297
复制
发表时间：
2001-02-05
影响因子：
15.3
通讯作者：
Zinkernagel, R M
中科院分区：
文献类型：
--
作者：
Ciurea, A;Hunziker, L;Klenerman, P;Hengartner, H;Zinkernagel, R M
我们以前已经表明，中和抗体（nAbs）是淋巴细胞性脉络丛脑膜炎病毒感染的长期免疫控制的重要贡献者，特别是如果细胞毒性T细胞反应低或不存在。然而，由于表面糖蛋白基因内的突变，病毒从nAb应答中逃逸，随后可能使病毒持续存在。在这里，我们表明，大多数抗体逃逸病毒突变体保留其免疫原性。我们提出的证据表明，感染的主机安装有效的体液反应对新兴的中和逃逸突变体的失败与CD4+ T细胞反应性的快速丧失在建立病毒持久性。类似的机制可能有助于一些人类病原体的持续存在，如B肝炎病毒和丙型肝炎病毒，以及人类免疫缺陷病毒。
We have shown previously that neutralizing antibodies (nAbs) are important contributors to the long-term immune control of lymphocytic choriomeningitis virus infection, particularly if cytotoxic T cell responses are low or absent. Nevertheless, virus escape from the nAb response due to mutations within the surface glycoprotein gene may subsequently allow the virus to persist. Here we show that most of the antibody-escape viral mutants retain their immunogenicity. We present evidence that the failure of the infected host to mount effective humoral responses against emerging neutralization-escape mutants correlates with the rapid loss of CD4+ T cell responsiveness during the establishment of viral persistence. Similar mechanisms may contribute to the persistence of some human pathogens such as hepatitis B and C viruses, and human immunodeficiency virus.