Interferon alpha induces a stronger antiviral effect than interferon lambda in HBV/HDV infected humanized mice

被引：0

作者：

Duehren, Sarah ^{[1
]}

Uchida, Takuro ^{[2
,3
,4
]}

Tsuge, Masataka ^{[4
,5
,6
]}

Hiraga, Nobuhiko ^{[4
]}

Uprichard, Susan L. ^{[1
]}

Etzion, Ohad ^{[7
]}

Glenn, Jeffrey ^{[8
,9
,10
]}

Koh, Christopher ^{[11
]}

Heller, Theo ^{[11
]}

Cotler, Scott J. ^{[1
]}

Oka, Shiro

Chayama, Kazuaki ^{[12
,13
]}

Dahari, Harel

机构：

[1] Loyola Univ Chicago, Stritch Sch Med, Dept Med, Div Hepatol,Program Expt & Theoret Modeling, Maywood, IL USA

[2] Oita Univ, Fac Med, Dept Gastroenterol, Yufu, Japan

[3] Oita Univ, Res Ctr GLOBAL & LOCAL Infect Dis, Div Travel Med & Hlth, Yufu, Japan

[4] Hiroshima Univ, Res Ctr Hepatol & Gastroenterol, Hiroshima, Japan

[5] Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Dept Gastroenterol, Hiroshima, Japan

[6] Hiroshima Univ Hosp, Liver Ctr, Hiroshima, Japan

[7] Soroka Univ, Dept Gastroenterol & Liver Dis, Med Ctr, Beer Sheva, Israel

[8] Stanford Sch Med, Dept Med, Div Gastroenterol & Hepatol, Stanford, CA 94305 USA

[9] Stanford Sch Med, Dept Immunol, Div Microbiol, Stanford, CA USA

[10] Stanford Sch Med, Dept Immunol, Div Gastroenterol & Hepatol, Stanford, CA USA

[11] NIH, NIDDK, Liver Dis Branch, Bethesda, MD USA

[12] Hiroshima Inst Life Sci, Hiroshima, Japan

[13] RIKEN Ctr Integrat Med Sci, Yokohama, Japan

来源：

VIRUS RESEARCH | 2024年 / 349卷

基金：

美国国家卫生研究院;

关键词：

HBV DNA; HDV RNA; HBsAg; Human albumin; Humanized mice; Interferon alpha; Interferon lambda; HEPATITIS-B-VIRUS; KINETICS; DNA;

D O I：

10.1016/j.virusres.2024.199451

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Recent studies indicate that treatment of chronic hepatitis D virus (HDV) with either pegylated interferon (IFN)lambda or pegylated IFN alpha monotherapy leads to a dramatic decline in HDV RNA. Herein, we investigated the innate antiviral efficacy of IFN lambda and IFN alpha in humanized mice that lack an adaptive immune response. Humanized mice were either co-infected with hepatitis B virus (HBV) and HDV simultaneously, or HDV infection was performed subsequent to HBV infection (i.e., superinfected). After steady viral replication was achieved, mice received either IFN lambda (n = 6) or IFN alpha (n = 7) for 12 (or 13) weeks. Pretreatment median levels of serum HBV DNA (8.8 [IQR:0.2] log IU/ml), HDV RNA (9.8 [0.5] log IU/ml), HBsAg (4.0 [0.4] log IU/ml) and human albumin, hAlb (6.9 [0.1] log ng/mL) were similar between mice treated with IFN alpha or IFN lambda and between those coinfected versus superinfected. Compared to mice treated with IFN lambda, mice treated with IFN alpha had a significantly greater decline in HBV, HDV, and HBsAg levels. In conclusion, IFN alpha induces stronger inhibition of HBV and HDV than IFN lambda in humanized mice that lack an adaptive immune response. Further studies are needed to assess the respective role of the combined innate-and adaptive-immune systems in the treatment of HBV and HDV with IFN alpha and IFN lambda.

引用

页数：5

共 16 条

[1] Therapeutic shutdown of HBV transcripts promotes reappearance of the SMC5/6 complex and silencing of the viral genome in vivo [J].