Kazumoto Murata1, Jong-Hon Kang2, Shigeo Nagashima3, Takeshi Matsui2, Yoshiyasu Karino4, Yoshiya Yamamoto5, Tomofumi Atarashi6, Masatsugu Oohara7, Minoru Uebayashi7, Hidekatsu Sakata8, Keiji Matsubayashi9, Kazuaki Takahashi10, Masahiro Arai10, Shunji Mishiro10, Masaya Sugiyama11, Masashi Mizokami11, Hiroaki Okamoto3. 1. Department of Gastroenterology, Graduate School of Medical Sciences, International University of Health and Welfare, Nasushiobara, Japan; Genome Medical Science Project, National Center for Global Health and Medicine, Ichikawa, Japan. Electronic address: kmurata@iuhw.ac.jp. 2. Center for Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan. 3. Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke, Japan. 4. Department of Hepatology, Sapporo Kosei General Hospital, Sapporo, Japan. 5. Department of Gastroenterology, Hakodate Municipal Hospital, Hakodate, Japan. 6. Department of Gastroenterology, Obihiro Kosei Hospital, Obihiro, Japan. 7. Department of Gastroenterology and Oncology, Kitami Red Cross Hospital, Kitami, Japan. 8. Japanese Red Cross Hokkaido Block Blood Center, Sapporo, Japan. 9. Central Blood Institute, Blood Service Headquarters, Japanese Red Cross Society, Tokyo, Japan. 10. Department of Medical Sciences, Tokyo Shinagawa Hospital, Tokyo, Japan. 11. Genome Medical Science Project, National Center for Global Health and Medicine, Ichikawa, Japan.
Abstract
BACKGROUND AND AIM: Hepatitis E virus (HEV) is mainly transmitted orally, either waterborne or zoonotic foodborne. Intestinal viruses such as rotavirus are known to induce type III interferon (IFN) in the gastrointestinal (GI) tract where type III IFN dominantly functions in comparison with type I IFN. Therefore, the aim of this study is to investigate the significance of type III IFN (IFN-λ3) in acute hepatitis E. METHODS: IFN-λ3 and HEV RNA levels in the sera of patients with acute HEV infection and in the supernatant of HEV-inoculated cells were measured, using an in-house high-sensitivity method and reverse transcription-polymerase chain reaction, respectively. RESULTS: High serum IFN-λ3 levels were found in the early phase of acute HEV infection, which normalized after resolution. Interestingly, serum IFN-λ3 levels correlated well with serum HEV RNA titers in the same sera, both of which showed the peak before the robust increase of transaminases. In vitro experiments demonstrated that HEV replicated well in the cells with little IFN-λ3 induction (Caco-2, A549) and recombinant IFN-λ3 inhibited HEV replication in a dose-dependent manner. In contrast, in HT-29 cells, a colon cancer cell line, HEV poorly replicated and induced IFN-λ3 in a titer-dependent manner. CONCLUSIONS: These clinical and experimental observations suggest that HEV induced IFN-λ3 as a host innate immune response, which may play a protective role against HEV.
BACKGROUND AND AIM: Hepatitis E virus (HEV) is mainly transmitted orally, either waterborne or zoonotic foodborne. Intestinal viruses such as rotavirus are known to induce type III interferon (IFN) in the gastrointestinal (GI) tract where type III IFN dominantly functions in comparison with type I IFN. Therefore, the aim of this study is to investigate the significance of type III IFN (IFN-λ3) in acute hepatitis E. METHODS:IFN-λ3 and HEV RNA levels in the sera of patients with acute HEV infection and in the supernatant of HEV-inoculated cells were measured, using an in-house high-sensitivity method and reverse transcription-polymerase chain reaction, respectively. RESULTS: High serum IFN-λ3 levels were found in the early phase of acute HEV infection, which normalized after resolution. Interestingly, serum IFN-λ3 levels correlated well with serum HEV RNA titers in the same sera, both of which showed the peak before the robust increase of transaminases. In vitro experiments demonstrated that HEV replicated well in the cells with little IFN-λ3 induction (Caco-2, A549) and recombinant IFN-λ3 inhibited HEV replication in a dose-dependent manner. In contrast, in HT-29 cells, a colon cancer cell line, HEV poorly replicated and induced IFN-λ3 in a titer-dependent manner. CONCLUSIONS: These clinical and experimental observations suggest that HEV induced IFN-λ3 as a host innate immune response, which may play a protective role against HEV.
Authors: Harini Sooryanarain; C Lynn Heffron; Hassan M Mahsoub; Anna M Hassebroek; Bo Wang; Debin Tian; S Ansar Ahmed; Xiang-Jin Meng Journal: J Virol Date: 2022-09-14 Impact factor: 6.549