Innate immune mechanisms during hepatits C virus infections
The project is part of a continuous research effort to address the mechanisms by which RNA viruses affect autophagy and innate immune responses. RNA viruses include several viral species that are of global health concerns, such as hepatitis C virus (HCV), measles virus, and HIV-1. Autophagy has been shown to degrade proteins from RNA virus species. We have studied HCV and Sendai virus (SV) which is an RNA virus recognized by the same host sensor as HCV, i.e. the RNA helicase RIG-I. RIG-I is known to induce antiviral transcription necessary to fight infection. We have established methods to discriminate between autophagy induction and autophagic degradation. Our results show that the HCV-sensor RIG-I induces autophagy, acting through the mitochondrial adapter protein MAVS. Interestingly, viral proteins inhibited degradation of autophagic cargo. We are now studying host factors that are utilized by HCV and SV to inhibit autophagic degradation. Also, we have found that autophagy affects activation of Nrf2 during RNA virus infection. In parallel, we have initiated studies on autophagy in relation to HCV-induced liver pathogenesis, using biopsies from HCV-infected patients. Inflammation and pathology of liver tissue in these patients have been categorized according to international standards. Moreover, optimization for identifying autophagy components in diseased liver by using immunocytochemistry has been initiated.
Mulige konsekvenser for helsetjenesten kan være at man med tiden kan utvikle forbedrede legemidler for behandling av hepatitt C. Per idag benyttes kombinasjonsterapi med ribavirin og interferon-alfa. Omlag 70 - 80 % av pasientene med virus av genotype 2 eller 3, mens bare 30-40 % av dem med virus av genotype 1 blir kvitt viruset. Det er derfor behov for utvikling av nye legemdidler mot hepatitt C virus.
LysoPC and PAF Trigger Arachidonic Acid Release by Divergent Signaling Mechanisms in Monocytes.
J Lipids 2011;2011():532145. Epub 2011 sep 11
Toll-like receptor 3-elicited MAPK activation induces stabilization of interferon-ß mRNA.
Cytokine 2012 Mar;57(3):337-46. Epub 2011 des 24
A role for the autophagy cargo protein p62 in MAVS-mediated signaling
Toll2011 Meeting · Decoding Innate Immunity
A novel association between an innate immune protein and a cargo receptor of autophagy
Keystone Symposia Autophagy (D11)
The role of c-Src tyrosine kinase in antiviral immune responses
- juni 2011
- Marit W Anthonsen
Innate antiviral immunity - Mechanisms of the RIG-I-mediated response
- oktober 2011
- Marit W Anthonsen