Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Wild-type (wt) vesicular stomatitis virus (VSV) strains stimulate plasmacytoid dendritic cells (pDC) through Toll-like receptor 7 (TLR7) and its adaptor molecule, MyD88. Granulocyte-macrophage colony-stimulating factor-derived DC (G-DC), which do not express TLR7, are unresponsive to wt VSV due to inhibition of cellular gene expression by the matrix (M) protein. In contrast to its recombinant wt (rwt) counterpart, an M protein mutant of VSV, rM51R-M virus, stimulates maturation of G-DC independently of MyD88. These results suggest that, as in the case of G-DC, rM51R-M virus may stimulate pDC by mechanisms distinct from that by rwt virus. Studies presented here demonstrate that both rwt and rM51R-M viruses induced maturation of TLR7-positive DC derived by culture in the presence of Flt3L (F-DC), with the subsequent expression of type I interferon (IFN). F-DC are a mixture of myeloid (CD11b(+)) and plasmacytoid (B220(+)) DC, both of which respond to TLR7 ligands. Separated CD11b(+) and B220(+) F-DC responded to both rwt and rM51R-M viruses. Both viruses were also defective at inhibiting host gene expression in F-DC, including the expression of genes involved in the antiviral response. The data from F-DC generated from IFN receptor knockout mice demonstrated that the maturation of F-DC induced by rwt virus was dependent on the type I IFN response, while maturation induced by rM51R-M virus was partially dependent on this molecule. Therefore, activation of the type I IFN pathway appears to be important for not only inducing an antiviral response but also for stimulating maturation of F-DC upon virus infection. Importantly, F-DC from TLR7 and MyD88 knockout mice did not undergo maturation in response to rwt virus, while maturation induced by rM51R-M virus was largely independent of both molecules. These results indicate that although both viruses induce F-DC maturation, F-DC detect and respond to rM51R-M virus by means that are distinct from rwt virus. Specifically, this mutant virus appears capable of inducing DC maturation in a wide variety of DC subsets through TLR-dependent and independent mechanisms.
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PMID:Vesicular stomatitis virus M protein mutant stimulates maturation of Toll-like receptor 7 (TLR7)-positive dendritic cells through TLR-dependent and -independent mechanisms. 1914 11

Inhibition of host-directed gene expression by the matrix (M) protein of vesicular stomatitis virus (VSV) effectively blocks host antiviral responses, promotes virus replication, and disables the host cell. However, dendritic cells (DC) have the capacity to resist these effects and remain functional during VSV infection. Here, the mechanisms of DC resistance to M protein and their subsequent maturation were addressed. Flt3L-derived murine bone marrow dendritic cells (FDC), which phenotypically resemble resident splenic DC, continued to synthesize cellular proteins and matured during single-cycle (high-multiplicity) and multicycle (low-multiplicity) infection with VSV. Granulocyte-macrophage colony-stimulating factor (GM-CSF)-derived myeloid DC (GDC), which are susceptible to M protein effects, were nevertheless capable of maturing, but the response was delayed and occurred only during multicycle infection. FDC resistance was manifested early and was type I interferon (IFN) receptor (IFNAR) and MyD88 independent, but sustained resistance required IFNAR. MyD88-dependent signaling contributed to FDC maturation during single-cycle infection but was dispensable during multicycle infection. Similar to FDC, splenic DC were capable of maturing in vivo during the first 24 h of infection with VSV, and neither Toll-like receptor 7 (TLR7) nor MyD88 was required. We conclude that FDC resistance to M protein is controlled by an intrinsic, MyD88-independent mechanism that operates early in infection and is augmented later in infection by type I IFN. In contrast, while GDC are not intrinsically resistant, they can acquire resistance during multicycle infection. In vivo, splenic DC resist the inhibitory effects of VSV, and as in multicycle FDC infection, MyD88-independent signaling events control their maturation.
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PMID:Preservation of dendritic cell function during vesicular stomatitis virus infection reflects both intrinsic and acquired mechanisms of resistance to suppression of host gene expression by viral M protein. 2398 80