IFN-λ3 as a host immune response in acute hepatitis E virus infection.
Acute Disease
Adult
Caco-2 Cells
Cell Line, Tumor
Female
Hepatitis E
/ enzymology
Hepatitis E virus
/ genetics
Humans
Immunity, Innate
Interferon-alpha
/ blood
Interferon-beta
/ blood
Interferons
/ blood
Male
Middle Aged
Recombinant Proteins
Transaminases
/ blood
Virus Replication
/ drug effects
Interferon Lambda
Acute hepatitis E
Innate immunity
Interferon-λ3
Journal
Cytokine
ISSN: 1096-0023
Titre abrégé: Cytokine
Pays: England
ID NLM: 9005353
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
21
12
2018
revised:
31
07
2019
accepted:
19
08
2019
pubmed:
30
8
2019
medline:
21
5
2021
entrez:
30
8
2019
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 31465972
pii: S1043-4666(19)30245-5
doi: 10.1016/j.cyto.2019.154816
pii:
doi:
Substances chimiques
Interferon-alpha
0
Recombinant Proteins
0
Interferon-beta
77238-31-4
Interferons
9008-11-1
Transaminases
EC 2.6.1.-
Interferon Lambda
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
154816Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.