The host antiviral innate immunity mainly relies on host pattern recognition receptors (PRR) and downstream interferon (IFN) signaling. Host PRR for RNA viruses include Toll-like receptors (TLR) and Retinoic acid-inducible gene I (RIG-I) like receptors (RLR). Activation of both TLR and RLR pathways can eventually lead to the secretion of type I IFNs, which can modulate both innate and adaptive immune responses against viral pathogens, including hepatitis E virus (HEV). HEV causes acute hepatitis in humans and has been responsible for several outbreaks of hepatitis across the world. Currently, no commercial vaccine is available for the prevention of HEV infection in any country except China. HEV biology and pathogenesis as well as its responses to host innate immunity are poorly understood, though other hepatitis viruses, including the hepatitis A, B and C viruses, have been much better studied. In this study, how HEV interferes with IFN induction and IFN-activated signaling had been examined. Results showed that the protein encoded by HEV ORF1 can inhibit type I IFN synthesis and downstream JAK/STAT signaling pathway. However, the HEV ORF3 product is able to enhance RIG-I-mediated signaling to a certain extent. These data suggest that HEV proteins interfere with the host innate immune response and may exert the diverse roles depending on the stage and/or context of infection. These studies contribute to a better understanding of HEV pathogenesis and may facilitate a strategy development for the prevention and control of HEV infection.
|Commitee:||Belov, Georgiy, Pal, Utpal, Song, Wenxia, Zhu, Xiaoping|
|School:||University of Maryland, College Park|
|Department:||Veterinary Medical Science|
|School Location:||United States -- Maryland|
|Source:||DAI-B 76/03(E), Dissertation Abstracts International|
|Subjects:||Public health, Virology, Epidemiology|
|Keywords:||Hepatitis e virus, Innate immunity, Interferons, Retinoic acid-inducible gene i like receptors|
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