Hasenkrug K J, Brooks D M, Dittmer U
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA.
J Virol. 1998 Aug;72(8):6559-64. doi: 10.1128/JVI.72.8.6559-6564.1998.
Reactivations of persistent viral infections pose a significant medical problem in immunocompromised cancer, transplant, and AIDS patients, yet little is known about how persistent viral infections are immunologically controlled. Here we describe a mouse model for investigating the role of the immune response in controlling a persistent retroviral infection. We demonstrate that, following recovery from acute Friend virus infection, a small number of B cells evade immunological destruction and harbor persistent virus. In vivo depletions of T-cell subsets in persistently infected mice revealed a critical role for CD4(+) T cells in controlling virus replication, spread to the erythroid lineage, and induction of erythroleukemia. The CD4(+) T-cell effect was independent of CD8(+) T cells and in some cases was also independent of virus-neutralizing antibody responses. Thus, the CD4(+) T cells may have had a direct antiviral effect. These results may have relevance for human immunodeficiency virus (HIV) infections where loss of CD4(+) T cells is associated with an increase in HIV replication, reactivation of persistent viruses, and a high incidence of virus-associated cancers.
持续性病毒感染的重新激活在免疫功能低下的癌症患者、移植患者和艾滋病患者中构成了一个重大的医学问题，但对于持续性病毒感染是如何受到免疫控制的，人们知之甚少。在此，我们描述了一种用于研究免疫反应在控制持续性逆转录病毒感染中作用的小鼠模型。我们证明，在从急性Friend病毒感染中恢复后，少数B细胞逃避免疫破坏并携带持续性病毒。对持续性感染小鼠体内T细胞亚群的清除揭示了CD4(+) T细胞在控制病毒复制、向红细胞谱系扩散以及诱导红白血病方面的关键作用。CD4(+) T细胞的作用独立于CD8(+) T细胞，在某些情况下也独立于病毒中和抗体反应。因此，CD4(+) T细胞可能具有直接的抗病毒作用。这些结果可能与人类免疫缺陷病毒（HIV）感染相关，在HIV感染中，CD4(+) T细胞的丧失与HIV复制增加、持续性病毒的重新激活以及病毒相关癌症的高发病率有关。
