Enforced viral replication activates adaptive immunity and is essential for the control of a cytopathic virus
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Enforced viral replication activates adaptive immunity and is essential for the control of a cytopathic virus. / Honke, Nadine; Shaabani, Namir; Cadeddu, Giuseppe; Sorg, Ursula R; Zhang, Dong-Er; Trilling, Mirko; Klingel, Karin; Sauter, Martina; Kandolf, Reinhard; Gailus, Nicole; van Rooijen, Nico; Burkart, Christoph; Baldus, Stephan E; Grusdat, Melanie; Löhning, Max; Hengel, Hartmut; Pfeffer, Klaus; Tanaka, Masato; Häussinger, Dieter; Recher, Mike; Lang, Philipp A; Lang, Karl S.
In: NAT IMMUNOL, Vol. 13, No. 1, 20.11.2011, p. 51-57.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
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
PY - 2011/11/20
Y1 - 2011/11/20
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.
KW - Adaptive Immunity
KW - Animals
KW - Antigen Presentation/immunology
KW - Antigens, Viral/immunology
KW - Cell Line, Transformed
KW - Cricetinae
KW - Dendritic Cells/immunology
KW - Endopeptidases/metabolism
KW - Lymphotoxin beta Receptor/metabolism
KW - Macrophages/immunology
KW - Membrane Glycoproteins/metabolism
KW - Mice
KW - Mice, 129 Strain
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Receptors, Immunologic/metabolism
KW - Rhabdoviridae Infections/immunology
KW - Sialic Acid Binding Ig-like Lectin 1
KW - Ubiquitin Thiolesterase
KW - Vesicular stomatitis Indiana virus/immunology
KW - Virus Replication/immunology
U2 - 10.1038/ni.2169
DO - 10.1038/ni.2169
M3 - SCORING: Journal article
C2 - 22101728
VL - 13
SP - 51
EP - 57
JO - NAT IMMUNOL
JF - NAT IMMUNOL
SN - 1529-2908
IS - 1
ER -