Borrow P, Tishon A, Oldstone M B
Department of Neuropharmacology, Scripps Clinic and Research Foundation, La Jolla, California 92037.
J Exp Med. 1991 Jul 1;174(1):203-12. doi: 10.1084/jem.174.1.203.
For viruses to establish persistent infections in their hosts, they must possess some mechanism for evading clearance by the immune system. When inoculated into adult immunocompetent mice, wild-type lymphocytic choriomeningitis virus (LCMV ARM) induces a CD8(+)-mediated cytotoxic T lymphocyte (CTL) response that clears the infection within 7-14 d (CTL+ [P-]). By contrast, variant viruses isolated from lymphoid tissues of persistently infected mice fail to induce a CTL response and are thus able to establish a persistent infection in adult mice (CTL- [P+]). This report compares the interaction of CTL+ (P-) and CTL- (P+) viruses with cells of the immune system. Both types of virus initially bind to 2-4% of CD4+ and CD8+ T lymphocytes and replicate within cells of both subsets. The replication of CTL- (P+) and CTL+ (P-) viruses in lymphocytes in vivo is similar for the first 5 d after initiating infection. Thereafter, in mice infected with CTL- (P+) variants, lymphocytes retain viral genetic information, and infectious virus can be recovered throughout the animals' lives. In contrast, when adult mice are infected with wild-type CTL+ (P-) LCMV ARM, virus is not recovered from lymphocytes for greater than 7 d after infection. A CD8(+)-mediated anti-LCMV CTL response is induced in such mice. Clearance of infected lymphocytes is produced by these LCMV-specific CTLs, as shown by their ability to lyse lymphocytes expressing LCMV determinants in vitro and the fact that depletion of CD8+ lymphocytes before infection with CTL+ (P-) viruses results in levels of infected lymphocytes similar to those found in undepleted CTL- (P+)-infected mice. Hence, CTL-mediated lysis of T lymphocytes carrying infectious virus is a critical factor determining whether virus persists or the infection is terminated.
病毒要在宿主中建立持续性感染，就必须具备某种机制来逃避免疫系统的清除。将野生型淋巴细胞性脉络丛脑膜炎病毒（LCMV ARM）接种到成年免疫功能正常的小鼠体内时，会诱导CD8(+)介导的细胞毒性T淋巴细胞（CTL）反应，该反应会在7 - 14天内清除感染（CTL+ [P-]）。相比之下，从持续感染小鼠的淋巴组织中分离出的变异病毒无法诱导CTL反应，因此能够在成年小鼠中建立持续性感染（CTL- [P+]）。本报告比较了CTL+（P-）和CTL-（P+）病毒与免疫系统细胞的相互作用。两种病毒最初都与2 - 4%的CD4+和CD8+ T淋巴细胞结合，并在这两个亚群的细胞内复制。在感染开始后的前5天，CTL-（P+）和CTL+（P-）病毒在体内淋巴细胞中的复制情况相似。此后，在感染CTL-（P+）变异株的小鼠中，淋巴细胞保留了病毒遗传信息，并且在动物的整个生命过程中都能回收感染性病毒。相反，当成年小鼠感染野生型CTL+（P-）LCMV ARM时，感染后7天以上淋巴细胞中就无法再回收病毒。此类小鼠会诱导产生CD8(+)介导的抗LCMV CTL反应。这些LCMV特异性CTL会清除被感染的淋巴细胞，这体现在它们能够在体外裂解表达LCMV决定簇的淋巴细胞，以及在感染CTL+（P-）病毒之前耗尽CD8+淋巴细胞会导致感染淋巴细胞水平与未耗尽的CTL-（P+）感染小鼠中的水平相似。因此，CTL介导的对携带感染性病毒的T淋巴细胞的裂解是决定病毒是持续存在还是感染被终止的关键因素。
