Publication Date:
2014-09-06
Description:
Pathogens traverse multiple barriers during infection, including cell membranes. We found that during this transition, pathogens carried covalently attached complement C3 into the cell, triggering immediate signaling and effector responses. Sensing of C3 in the cytosol activated mitochondrial antiviral signaling (MAVS)-dependent signaling cascades and induced proinflammatory cytokine secretion. C3 also flagged viruses for rapid proteasomal degradation, preventing their replication. This system could detect both viral and bacterial pathogens but was antagonized by enteroviruses, such as rhinovirus and poliovirus, which cleave C3 using their 3C protease. The antiviral rupintrivir inhibited 3C protease and prevented C3 cleavage, rendering enteroviruses susceptible to intracellular complement sensing. Thus, complement C3 allows cells to detect and disable pathogens that have invaded the cytosol.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172439/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172439/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tam, Jerry C H -- Bidgood, Susanna R -- McEwan, William A -- James, Leo C -- 281627/European Research Council/International -- MC_U105181010/Medical Research Council/United Kingdom -- U105181010/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2014 Sep 5;345(6201):1256070. doi: 10.1126/science.1256070. Epub 2014 Sep 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council Laboratory of Molecular Biology, Division of Protein and Nucleic Acid Chemistry, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK. ; Medical Research Council Laboratory of Molecular Biology, Division of Protein and Nucleic Acid Chemistry, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK. lcj@mrc-lmb.cam.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25190799" target="_blank"〉PubMed〈/a〉
Keywords:
Adenoviridae/*immunology
;
Adenovirus Infections, Human/*immunology
;
Animals
;
Antibodies, Viral/immunology
;
Complement C3/*immunology
;
Cytokines/biosynthesis/genetics
;
Dogs
;
HEK293 Cells
;
Host-Pathogen Interactions/*immunology
;
Humans
;
*Immunity, Innate
;
Interferon Regulatory Factors/metabolism
;
NF-kappa B/metabolism
;
Proteasome Endopeptidase Complex/metabolism
;
Ribonucleoproteins/genetics/metabolism
;
Signal Transduction
;
Transcription Factor AP-1/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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