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

Nadine Honke, Namir Shaabani, Giuseppe Cadeddu, Ursula R. Sorg, Dong Er Zhang, Mirko Trilling, Karin Klingel, Martina Sauter, Reinhard Kandolf, Nicole Gailus, Nico Van Rooijen, Christoph Burkart, Stephan E. Baldus, Melanie Grusdat, Max Löhning, Hartmut Hengel, Klaus Pfeffer, Masato Tanaka, Dieter Häussinger, Mike RecherPhilipp A. Lang, Karl S. Lang*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

165 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)51-57
Number of pages7
JournalNature Immunology
Volume13
Issue number1
DOIs
Publication statusPublished - Jan 2012
Externally publishedYes

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