Sevilla N, Kunz S, Holz A, Lewicki H, Homann D, Yamada H, Campbell K P, de La Torre J C, Oldstone M B
Department of Neuropharmacology, Division of Virology, The Scripps Research Institute, La Jolla, California 92037, USA.
J Exp Med. 2000 Nov 6;192(9):1249-60. doi: 10.1084/jem.192.9.1249.
Among cells of the immune system, CD11c(+) and DEC-205(+) splenic dendritic cells primarily express the cellular receptor (alpha-dystroglycan [alpha-DG]) for lymphocytic choriomeningitis virus (LCMV). By selection, strains and variants of LCMV that bind alpha-DG with high affinity are associated with virus replication in the white pulp, show preferential replication in a majority of CD11c(+) and DEC-205(+) cells, cause immunosuppression, and establish a persistent infection. In contrast, viral strains and variants that bind with low affinity to alpha-DG are associated with viral replication in the red pulp, display minimal replication in CD11c(+) and DEC-205(+) cells, and generate a robust anti-LCMV cytotoxic T lymphocyte response that clears the virus infection. Differences in binding affinities can be mapped to a single amino acid change in the viral glycoprotein 1 ligand that binds to alpha-DG. These findings indicate that receptor-virus interaction on dendritic cells in vivo can be an essential step in the initiation of virus-induced immunosuppression and viral persistence.
在免疫系统细胞中，CD11c(+)和DEC-205(+)脾树突状细胞主要表达淋巴细胞性脉络丛脑膜炎病毒（LCMV）的细胞受体（α- dystroglycan [α-DG]）。通过筛选，与α-DG高亲和力结合的LCMV毒株和变体与白髓中的病毒复制相关，在大多数CD11c(+)和DEC-205(+)细胞中显示出优先复制，导致免疫抑制，并建立持续感染。相反，与α-DG低亲和力结合的病毒毒株和变体与红髓中的病毒复制相关，在CD11c(+)和DEC-205(+)细胞中显示出最小程度的复制，并产生强大的抗LCMV细胞毒性T淋巴细胞反应以清除病毒感染。结合亲和力的差异可映射到与α-DG结合的病毒糖蛋白1配体中的单个氨基酸变化。这些发现表明，体内树突状细胞上的受体-病毒相互作用可能是病毒诱导的免疫抑制和病毒持续存在起始的关键步骤。
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