Enforced viral replication activates adaptive immunity and is essential for the control of a cytopathic virus

Nat Immunol. 2011 Nov 20;13(1):51-7. doi: 10.1038/ni.2169.


The innate immune system limits viral replication via type I interferon and also induces the presentation of viral antigens to cells of the adaptive immune response. Using infection of mice with vesicular stomatitis virus, we analyzed how the innate immune system inhibits viral propagation but still allows the presentation of antigen to cells of the adaptive immune response. We found that expression of the gene encoding the inhibitory protein Usp18 in metallophilic macrophages led to lower type I interferon responsiveness, thereby allowing locally restricted replication of virus. This was essential for the induction of adaptive antiviral immune responses and, therefore, for preventing the fatal outcome of infection. In conclusion, we found that enforced viral replication in marginal zone macrophages was an immunological mechanism that ensured the production of sufficient antigen for effective activation of the adaptive immune response.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity*
  • Animals
  • Antigen Presentation / immunology
  • Antigens, Viral / immunology
  • Cell Line, Transformed
  • Cricetinae
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Dendritic Cells / virology
  • Endopeptidases / metabolism
  • Lymphotoxin beta Receptor / metabolism
  • Macrophages / immunology
  • Macrophages / metabolism
  • Macrophages / virology
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Immunologic / metabolism
  • Rhabdoviridae Infections / immunology*
  • Sialic Acid Binding Ig-like Lectin 1
  • Ubiquitin Thiolesterase
  • Vesicular stomatitis Indiana virus / immunology*
  • Virus Replication / immunology*


  • Antigens, Viral
  • Lymphotoxin beta Receptor
  • Membrane Glycoproteins
  • Receptors, Immunologic
  • Sialic Acid Binding Ig-like Lectin 1
  • Siglec1 protein, mouse
  • Endopeptidases
  • Usp18 protein, mouse
  • Ubiquitin Thiolesterase