Matrix protein mediated shutdown of host cell metabolism limits vesicular stomatitis virus-induced interferon-alpha responses to plasmacytoid dendritic cells |
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Authors: | Zoe Waibler Claudia N. Detje John C. Bell Ulrich Kalinke |
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Affiliation: | aDivision of Immunology, Paul-Ehrlich-Institut, D-63225 Langen, Germany;bDepartment of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5 |
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Abstract: | Upon infection with many different viruses, plasmacytoid dendritic cells (pDC) produce large amounts of type I interferon (IFN-/β). To address why upon vesicular stomatitis virus (VSV) infection pDC, but not conventional myeloid DC (mDC), are induced to produce IFN-, pDC and mDC were differentiated from bone marrow cells (BM-DC). Upon VSV infection BM-pDC produced IFN-, whereas BM-mDC did not. Notably, upon infection with VSV-M2, a VSV variant expressing a M51R mutant matrix (M) protein that showed a reduced sequestration of host cell metabolism, BM-pDC and BM-mDC mounted massive IFN- responses. Both DC subsets showed comparable RNA levels of retinoic acid inducible gene-I (RIG-I) and Toll-like receptor (TLR) 7 and were able to respond upon triggering with double-stranded RNA (dsRNA) or single-stranded RNA (ssRNA) analogs. Moreover, upon VSV-M2 infection IFN- production by both DC subsets was largely dependent on viral replication. Interestingly, upon virus infection BM-pDC, but not BM-mDC, up-regulated mRNA levels of nuclear export factors Nup96/98, probably reflecting cellular mechanisms to circumvent viral escape strategies. Collectively, these results indicated that cell types induced to produce IFN- upon viral infection are not primarily defined by cellular receptor configurations but rather by complex virus/host cell interactions. |
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Keywords: | Dendritic cells Interferons Matrix protein Viral escape VSV |
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