1, 2 Viruses CP-673451 purchase have evolved different mechanisms to inhibit type I IFN response and block various aspects of the signaling

pathway, thus escaping the host immune response and causing infection. Hepatitis E, caused by hepatitis E virus (HEV), is an emerging public health problem in both developing and developed countries. Hepatitis E mostly manifests as a self-limiting, icteric hepatitis in most individuals. However, substantially high mortality rates of as much as 20% are observed in pregnant women.3 Furthermore, organ transplant recipients, as well as human immunodeficiency virus (HIV)-infected and other immunocompromised individuals, run the risk of developing chronic liver disease when infected with HEV.4 Treatment of chronically infected patients with pegylated interferon-α2a/α2b or ribavirin for 3-12 months has been shown to achieve

a sustained virological response for 3-6 months after completion of the therapy.5, 6 HEV is a nonenveloped virus with a single positive-sense RNA genome of approximately 7.2 kb and is classified in the Hepevirus genus within the family Hepeviridae.3 The viral RNA consists of a short 5′ noncoding region (NCR), three open reading frames (ORFs), FGFR inhibitor and a 3′ NCR. A cap structure has been identified at the 5′ end of the viral genome, which may play a role in the initiation of HEV replication.7 ORF1, located at the 5′ end of the genome, encodes nonstructural polyproteins that are involved in viral

replication.8, 9 ORF2, located at 上海皓元医药股份有限公司 the 3′ end of the genome, encodes the viral capsid protein, which plays an important role in viral immune response.10 ORF3 encodes a cytoskeleton-associated phosphoprotein11 that is responsible for virion egress from infected cells and is essential for virus infectivity in vivo, although it is not required for virus infection in vitro.12 Viruses have been reported to influence the IFN regulatory pathway,13, 14 but effects of HEV on IFN signaling have not been studied so far because of the lack of an efficient HEV cell culture system or a small animal model of infection. Propagation and production of HEV in vitro have been attempted in many cell lines, but culturing HEV has proven to be difficult.15 Recently, successful propagation of HEV in A549 cells, a human lung adenocarcinoma epithelial cell line, was reported.15, 16 In this study, we describe the generation of an A549 cell line (HEV-A549) persistently infected with the genotype 3 HEV strain. Using this cell line, we investigated whether HEV inhibits IFN-α signaling.