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 Recher; Philipp A. Lang; Karl S. Lang

doi:10.1038/ni.2169

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 journal › Article › Research › peer-review

186 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 language	English
Pages (from-to)	51-57
Number of pages	7
Journal	Nature Immunology
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/ni.2169
Publication status	Published - Jan 2012
Externally published	Yes

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Honke, N., Shaabani, N., Cadeddu, G., Sorg, U. R., Zhang, D. E., Trilling, M., Klingel, K., Sauter, M., Kandolf, R., Gailus, N., Van Rooijen, N., Burkart, C., Baldus, S. E., Grusdat, M., Löhning, M., Hengel, H., Pfeffer, K., Tanaka, M., Häussinger, D., ... Lang, K. S. (2012). Enforced viral replication activates adaptive immunity and is essential for the control of a cytopathic virus. Nature Immunology, 13(1), 51-57. https://doi.org/10.1038/ni.2169

@article{2508222509204c29a31858f176fa578a,

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

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.",

author = "Nadine Honke and Namir Shaabani and Giuseppe Cadeddu and Sorg, {Ursula R.} and Zhang, {Dong Er} and Mirko Trilling and Karin Klingel and Martina Sauter and Reinhard Kandolf and Nicole Gailus and {Van Rooijen}, Nico and Christoph Burkart and Baldus, {Stephan E.} and Melanie Grusdat and Max L{\"o}hning and Hartmut Hengel and Klaus Pfeffer and Masato Tanaka and Dieter H{\"a}ussinger and Mike Recher and Lang, {Philipp A.} and Lang, {Karl S.}",

note = "Funding Information: We thank D. Kolakofsky (University of Geneva) for VSV; and K. Sch{\"a}ttel for technical support. Supported by the Alexander von Humboldt Foundation (SKA-2008 to K.S.L. and SKA-2010 to P.A.L.), Collaborative Research Center SFB575, Experimental Hepatology (coordinator, D.H.; Deutsche Forschungsgemeinschaft grant LA1419/3-1 to K.S.L. and SFB-TR19 to K.K. and R.K.; FOR729 to K.P.; SFB/Transregio 60 (coordinator, M. Roggendorf), the MOI Manchot Graduate School (J{\"u}rgen Manchot Foundation), the Swiss National Science Foundation (PASMP3-127678/1 to M.R.) and the US National Institutes of Health (R01 HL091549 for Usp18-related work in the D.-E.Z. laboratory).",

year = "2012",

month = jan,

doi = "10.1038/ni.2169",

language = "English",

volume = "13",

pages = "51--57",

journal = "Nature Immunology",

issn = "1529-2908",

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Honke, N, Shaabani, N, Cadeddu, G, Sorg, UR, Zhang, DE, Trilling, M, Klingel, K, Sauter, M, Kandolf, R, Gailus, N, Van Rooijen, N, Burkart, C, Baldus, SE, Grusdat, M, Löhning, M, Hengel, H, Pfeffer, K, Tanaka, M, Häussinger, D, Recher, M, Lang, PA & Lang, KS 2012, 'Enforced viral replication activates adaptive immunity and is essential for the control of a cytopathic virus', Nature Immunology, vol. 13, no. 1, pp. 51-57. https://doi.org/10.1038/ni.2169

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T1 - Enforced viral replication activates adaptive immunity and is essential for the control of a cytopathic virus

AU - Honke, Nadine

AU - Shaabani, Namir

AU - Cadeddu, Giuseppe

AU - Sorg, Ursula R.

AU - Zhang, Dong Er

AU - Trilling, Mirko

AU - Klingel, Karin

AU - Sauter, Martina

AU - Kandolf, Reinhard

AU - Gailus, Nicole

AU - Van Rooijen, Nico

AU - Burkart, Christoph

AU - Baldus, Stephan E.

AU - Grusdat, Melanie

AU - Löhning, Max

AU - Hengel, Hartmut

AU - Pfeffer, Klaus

AU - Tanaka, Masato

AU - Häussinger, Dieter

AU - Recher, Mike

AU - Lang, Philipp A.

AU - Lang, Karl S.

N1 - Funding Information: We thank D. Kolakofsky (University of Geneva) for VSV; and K. Schättel for technical support. Supported by the Alexander von Humboldt Foundation (SKA-2008 to K.S.L. and SKA-2010 to P.A.L.), Collaborative Research Center SFB575, Experimental Hepatology (coordinator, D.H.; Deutsche Forschungsgemeinschaft grant LA1419/3-1 to K.S.L. and SFB-TR19 to K.K. and R.K.; FOR729 to K.P.; SFB/Transregio 60 (coordinator, M. Roggendorf), the MOI Manchot Graduate School (Jürgen Manchot Foundation), the Swiss National Science Foundation (PASMP3-127678/1 to M.R.) and the US National Institutes of Health (R01 HL091549 for Usp18-related work in the D.-E.Z. laboratory).

PY - 2012/1

Y1 - 2012/1

N2 - 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.

AB - 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.

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DO - 10.1038/ni.2169

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VL - 13

SP - 51

EP - 57

JO - Nature Immunology

JF - Nature Immunology

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ER -

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

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