A novel TLR3 inhibitor encoded by African swine fever virus (ASFV)

African swine fever virus (ASFV) encodes proteins that manipulate important host antiviral mechanisms. Bioinformatic analysis of the ASFV genome revealed ORF I329L, a gene without any previous functional characterization as a possible inhibitor of TLR signaling. We demonstrate that ORF I329L encodes...

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Bibliographic Details
Published in:Archives of virology 2011-04, Vol.156 (4), p.597-609
Main Authors: de Oliveira, V. L., Almeida, S. C. P., Soares, H. R., Crespo, A., Marshall-Clarke, S., Parkhouse, R. M. E.
Format: Article
Language:English
Subjects:
African swine fever
African swine fever virus
African Swine Fever Virus - immunology
African Swine Fever Virus - pathogenicity
Animals
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Cell Line
Chemokine CCL5 - antagonists & inhibitors
Cytokines
Enzymes
Fundamental and applied biological sciences. Psychology
Genes
Genetic engineering
Glycoproteins - metabolism
Hogs
Humans
Immune Evasion
Infections
Infectious Diseases
Interferon
Interferon Regulatory Factor-3 - antagonists & inhibitors
Interferon-beta - antagonists & inhibitors
Invertebrates
Medical Microbiology
Mice
Microbiology
Miscellaneous
NF-kappa B - antagonists & inhibitors
Original
Original Article
Pathogens
Proteins
Receptors, Immunologic - antagonists & inhibitors
Toll-Like Receptor 3 - antagonists & inhibitors
Transcription factors
Tumor necrosis factor-TNF
Viral infections
Viral Proteins - metabolism
Virology
Virulence Factors - metabolism
Viruses
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Description
Summary:African swine fever virus (ASFV) encodes proteins that manipulate important host antiviral mechanisms. Bioinformatic analysis of the ASFV genome revealed ORF I329L, a gene without any previous functional characterization as a possible inhibitor of TLR signaling. We demonstrate that ORF I329L encodes a highly glycosylated protein expressed in the cell membrane and on its surface. I329L also inhibited dsRNA-stimulated activation of NFκB and IRF3, two key players in innate immunity. Consistent with this, expression of I329L protein also inhibited the activation of interferon-β and CCL5. Finally, overexpression of TRIF reversed I329L-mediated inhibition of both NFκB and IRF3 activation. Our results suggest that TRIF, a key MyD88-independent adaptor molecule, is a possible target of this viral host modulation gene. The demonstration of an ASFV host evasion molecule inhibiting TLR responses is consistent with the ability of this virus to infect vertebrate and invertebrate hosts, both of which deploy innate immunity controlled by conserved TLR systems.
ISSN:0304-8608
1432-8798
DOI:10.1007/s00705-010-0894-7