Chronic hepatitis C virus (HCV) infection is established in 80% of infected individuals and leads to cirrhosis, hepatocellular carcinoma (HCC) and end-stage liver disease. Despite new direct-acting antivirals (DAA), treatment failures, reinfection rates after clearance or treatment, viral resistance, treatment costs and the lack of a vaccine challenge over 170 million infected people infected worldwide and about 1% of the Canadian population.
It is imperative that our limited understanding of HCV immunopathogenesis and the long term immunological effects of chronic infection and potent DAAs be improved. An effective immune responses to HCV includes anti-viral cytotoxic CD8+ T-cell (CTL) activity, which is impaired in chronic infection. We identified generalized blood/liver CTL impairment in chronic HCV mono-infection and HCV-HIV co-infection (the #1 co-morbidity in 25% of HIV+ individuals). Co-infection with HCV and HIV is of particular concern as individuals experience faster liver disease progression and dual causes of CD8+ T-cell deficiency from both viruses.
Our research suggests that chronic HCV infection is damaging host immune systems and the consequences of this have not been investigated in depth. We will focus on identifying potential associations of this immunodeficiency with HCV infection, treatments, level of liver fibrosis and the development of HCC. Our research aims to ultimately improve chronic HCV infection care in Canada and beyond, and may provide insight into other immunity-damaging chronic diseases (e.g. HIV, malaria, helminthes, autoimmunity).
For more information visit:
http://www.crawleylab.ca/
Last 3 years:
2021
1. Ali H., Caballero R., Iqbal S., Gajnayaka N., Ahmed D., Dong S., Vranjkovic V., Crawley AM., Angel JB., Cassol E., Kumar A. Selective killing of human M1 macrophages by Smac mimetics alone and M2 macrophages by Smac mimetics and caspase inhibition. J. Leuk. Biol. 2021.
2020
2. Côté, SC., Burke Schinkel, SC., Berthoud TK., Barros PO., Sanchez-Vidales M., Davidson AM., Crawley AM., Angel JB. IL-7 induces sCD127 release and mCD127 downregulation in human CD8+ T cells by distinct yet overlapping mechanisms, both of which are impaired in HIV infection. Eur. J. Immunol., 2020. 50:1537-49.
3. Li J., Casey JL., Greenwald ZR., Yasseen AS., Dickie M., Feld JJ., Cooper CL., Crawley AM. The 9th Canadian Symposium on Hepatitis C Virus: Advances in HCV research and treatment towards elimination. Can. Liv. J. 2020.
4. Okwor CIA., Oh JS., Crawley AM., Cooper CL., Lee SH. Expression of inhibitory receptors on T and NK cells defines immunological phenotypes of HCV patients with advanced liver fibrosis. (iScience, 2020. 23(9): 101513 - impact factor: 5.8).
5. Odai KG., O’Dwyer C., Steenbergen R., Shaw T., Renner T., Ghorbani P., Langlois M-A., Crawley AM., Russell RS., Pezacki J., Tyrrell LD., Fullerton MD. In vitro hepatitis C virus infection and hepatic choline metabolism. Viruses, 12(1). pii: E108, 2020.
2019
6. Vranjkovic A., Deonarine F., Angel JB., Cooper CL., Crawley AM. Direct-Acting Antiviral Treatment of HCV Infection Does Not Resolve the Dysfunction of Circulating CD8+ T-Cells in Advanced Liver Disease. Frontiers Immunol., 10:1926, 2019.
7. Doyle MA., Lee T., Singer J., Crawley AM., Klein M., Cooper CL. Evaluation of safety and effectiveness of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Switch followed by Ledipasvir Sofosbuvir HCV Therapy in HIV-HCV Co-Infection. Open Forum Infectious Diseases 6(7). pii: ofz318 2019.
8. Ahmed F., Ibrahim A., Cooper CL., Kumar A., Crawley AM. Chronic Hepatitis C Virus Infection Impairs M1 Macrophage Differentiation and Contributes to CD8 + T-Cell Dysfunction. Cells 2019, 8:374 - Special Issue: Hepatitis C Virus and Host Interactions, by invitation.
9. Doyle M-A., Mulvihill E., Galanakis C., Crawley AM., Cooper CL. Influence of Ribavirin and the Cirrhotic State on Metabolic Measures in Hepatitis C Direct Acting Antiviral Treatment Recipients. Cells 2019, 8:252 - Special Issue: Hepatitis C Virus and Host Interactions, by invitation.
