Interferon stimulated immune profile changes in a humanized mouse model of HBV infection

Wang，Yaping1; Guo，Liliangzi1; Shi，Jingrong1; Li，Jingyun2; Wen，Yanling3; Gu，Guoming4; Cui，Jianping1; Feng，Chengqian1; Jiang，Mengling1; Fan，Qinghong1; Tang，Jingyan1; Chen，Sisi1; Zhang，Jun1; Zheng，Xiaowen1; Pan，Meifang1; Li，Xinnian5; Sun，Yanxia6; Zhang，Zheng3; Li，Xian4; Hu，Fengyu1; Zhang，Liguo2; Tang，Xiaoping1; Li，Feng1

2023-12-01

10.1038/s41467-023-43078-5

Nature Communications   影响因子和分区

2041-1723

The underlying mechanism of chronic hepatitis B virus (HBV) functional cure by interferon (IFN), especially in patients with low HBsAg and/or young ages, is still unresolved due to the lack of surrogate models. Here, we generate a type I interferon receptor humanized mouse (huIFNAR mouse) through a CRISPR/Cas9-based knock-in strategy. Then, we demonstrate that human IFN stimulates gene expression profiles in huIFNAR peripheral blood mononuclear cells (PBMCs) are similar to those in human PBMCs, supporting the representativeness of this mouse model for functionally analyzing human IFN in vivo. Next, we reveal the tissue-specific gene expression atlas across multiple organs in response to human IFN treatment; this pattern has not been reported in healthy humans in vivo. Finally, by using the AAV-HBV model, we test the antiviral effects of human interferon. Fifteen weeks of human PEG-IFNα2 treatment significantly reduces HBsAg and HBeAg and even achieves HBsAg seroconversion. We observe that activation of intrahepatic monocytes and effector memory CD8 T cells by human interferon may be critical for HBsAg suppression. Our huIFNAR mouse can authentically respond to human interferon stimulation, providing a platform to study interferon function in vivo. PEG-IFNα2 treatment successfully suppresses intrahepatic HBV replication and achieves HBsAg seroconversion.

SCI

英语

NI论文

其他

2-s2.0-85176768571

Scopus

1.Institute of infectious Diseases,Guangzhou Eighth People’s Hospital,Guangzhou Medical University,Guangzhou,8 Huaying Road, Baiyun District, Guangdong Province,China
2.CAS Key Laboratory of Infection and Immunity,Institute of Biophysics,Chinese Academy of Sciences,Beijing,China
3.Institute for Hepatology,National Clinical Research Center for Infectious Disease,Shenzhen Third People’s Hospital; The Second Affiliated Hospital,School of Medicine,Southern University of Science and Technology,Shenzhen,China
4.Guangzhou XY Biotechnology Co.,Ltd,Guangzhou,Room 2048, Building 1, No. 6, Nanjiang Second Road, Pearl River Street, Nansha District,China
5.Guangzhou Forevergen Medical Laboratory,Guangzhou,Room 802, No. 8, Luoxuan 3rd Road, Haizhu, Guangdong,China
6.Cytek (Shanghai) Biosciences Co,Ltd,Guangzhou,China

Wang，Yaping,Guo，Liliangzi,Shi，Jingrong,et al. Interferon stimulated immune profile changes in a humanized mouse model of HBV infection[J]. Nature Communications,2023,14(1).

Wang，Yaping.,Guo，Liliangzi.,Shi，Jingrong.,Li，Jingyun.,Wen，Yanling.,...&Li，Feng.(2023).Interferon stimulated immune profile changes in a humanized mouse model of HBV infection.Nature Communications,14(1).

Wang，Yaping,et al."Interferon stimulated immune profile changes in a humanized mouse model of HBV infection".Nature Communications 14.1(2023).