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Infection of Dendritic Cells by Lymphocytic Choriomeningitis Virus

  • N. Sevilla
  • S. Kunz
  • D. McGavern
  • M. B. A. Oldstone
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 276)

Abstract

Dendritic cells (DCs) comprise the major antigen-presenting cells (APCs) of the host, uniquely programmed to stimulate immunologically naïve T lymphocytes. Viruses that can target and disorder the function of these cells enjoy a selective advantage. The cellular receptor for lymphocytic choriomeningitis virus (LCMV), Lassa fever virus (LFV), and several other arenaviruses is α-dystroglycan (α-DG). Among cells of the immune system, CD11c+ and DEC-205+ DCs primarily and preferentially express α-DG. By selection, strains and variants of LCMV generated as quasi-species that bind α-DG with high affinity replicate in the majority of CD11c+ and DEC-205+ (>75%) DCs, causing a generalized immunosuppression, and establish a persistent infection. In contrast, viral strains and variants that bind with low affinity to α-DG display minimal replication in CD11c+ and DEC-205+ DCs (<10%), rarely replicate in the white pulp, and generate a robust anti-LCMV CTL response that clears the virus infection. Hence, receptor-virus interaction on DCs in vivo is an essential step in the initiation of virus-induced immunosuppression and viral persistence. Investigation into the mechanism of how virus-infected DCs cause immunosuppression reveals loss of MHC class II surface expression and costimulatory molecules on surface of such DCs. As a consequence DCs are unable to act as APCs, initiate immune responses, and have a defect in migration into the T cell area. These data indicate that LCMV infection influences DC maturation and migration, leading to decreased T cell stimulatory capacity of DCs, events essential for the initiation of immune responses. Because several other viruses known to cause immunosuppression (HIV, measles) interact with DCs, the observations noted here are likely a common selective mechanism by which viruses also are able to evade the host’s immune system.

Keywords

Human Immunodeficiency Virus Dendritic Cell Cellular Receptor Viral Persistence Lymphocytic Choriomeningitis Virus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2003

Authors and Affiliations

  • N. Sevilla
    • 1
  • S. Kunz
    • 1
  • D. McGavern
    • 1
  • M. B. A. Oldstone
    • 1
  1. 1.Department of Neuropharmacology, Division of VirologyThe Scripps Research InstituteLa JollaUSA

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