Accession

PRJCA017918

Title

Comprehensive immune profile changes to human interferon stimulation in normal and HBV-infected conditions in a humanized mouse

Relevance

Medical

Data types

Transcriptome or Gene expression

Organisms

Mus musculus
Homo sapiens

Description

The underlying mechanism of chronic hepatitis B virus (HBV) functional cure by interferon (IFN), especially in patients with low HBsAg or/and young ages, is still unresolved for lacking surrogate models. Here, we generated a type I interferon receptor humanized mouse (huIFNAR mouse) through a CRISPR/Cas9-based knock-in strategy. Then, we demonstrated that human IFN stimulated a similar gene expression profile of huIFNAR peripheral blood mononuclear cells (PBMC) to what in human PBMCs, supporting the representativeness of the novel mouse model in functionally analyzing human IFN in vivo. Next, we revealed a markedly tissue-specific gene expression atlas against human IFN treatment in the multiple organs less appreciated in healthy humans in vivo. Finally, using the AAV-HBV model, we test the antiviral effects of human interferon in this mouse. Fifteen-week human PEG-IFNα2 treatment significantly reduced HBsAg and HBeAg and even achieved HBsAg seroconversion. We observed that activation of intrahepatic monocytes and effector memory CD8 T cells by human interferon might be critical for HBsAg suppression. In conclusion, our novel huIFNAR mouse can authentically respond to human Interferon stimulation, providing a novel platform to study interferon function in vivo. The PEG-IFNα2 treatment successfully suppresses intrahepatic HBV replication and achieved HBsAg seroconversion in some mice.

Sample scope

Multiisolate

Release date

2023-09-24

Grants

Agency	program	Grant ID	Grant title
National Natural Science Foundation of China (NSFC)		81670536
National Natural Science Foundation of China (NSFC)		81770593
National Grand Program on Key Infectious Disease Control		2017ZX10202203-004-002
National Grand Program on Key Infectious Disease Control		2018ZX10301404-003-002
Guangzhou Science and Technology Project		202102080389
Guangzhou Science and Technology Project		202206080001
Guangzhou Science and Technology Project		2022-01-02-04-0087
Key-Area Research and Development Program of Guangdong Province		2022B1111020002
Guangdong Provincial Natural Science Foundation		2021A1515011287

Submitter

Feng Li (gz8h_lifeng@126.com)

Organization

Guangzhou Eighth People's Hospital, Guangzhou Medical University

Submission date

2023-06-25

Project Data

Resource name	Description
BioSample (36) show	-
SAMC2918997	RNA-Seq of HuIFNAR mice PBMC
SAMC2918996	RNA-Seq of HuIFNAR mice PBMC
SAMC2918995	RNA-Seq of HuIFNAR mice PBMC
SAMC2918994	RNA-Seq of HuIFNAR mice PBMC
SAMC2918993	RNA-Seq of HuIFNAR mice PBMC
SAMC2918992	RNA-Seq of HuIFNAR mice PBMC
SAMC2918991	RNA-Seq of HuIFNAR mice PBMC
SAMC2918990	RNA-Seq of HuIFNAR mice PBMC
SAMC2918989	RNA-Seq of HuIFNAR mice PBMC
SAMC2918988	RNA-Seq of HuIFNAR mice PBMC
SAMC2918987	RNA-Seq of HuIFNAR mice PBMC
SAMC2918986	RNA-Seq of HuIFNAR mice PBMC
SAMC2918985	RNA-Seq of HuIFNAR mice PBMC
SAMC2918984	RNA-Seq of HuIFNAR mice PBMC
SAMC2918983	RNA-Seq of HuIFNAR mice PBMC
SAMC2918982	RNA-Seq of HuIFNAR mice PBMC
SAMC2918981	RNA-Seq of HuIFNAR mice PBMC
SAMC2918980	RNA-Seq of HuIFNAR mice PBMC
SAMC2918979	RNA-Seq of wildtype mice PBMC
SAMC2918978	RNA-Seq of wildtype mice PBMC
SAMC2918977	RNA-Seq of wildtype mice PBMC
SAMC2918976	RNA-Seq of wildtype mice PBMC
SAMC2918975	RNA-Seq of wildtype mice PBMC
SAMC2918974	RNA-Seq of wildtype mice PBMC
SAMC2918973	RNA-Seq of wildtype mice PBMC
SAMC2918972	RNA-Seq of wildtype mice PBMC
SAMC2918971	RNA-Seq of wildtype mice PBMC
SAMC2918970	RNA-Seq of wildtype mice PBMC
SAMC2918969	RNA-Seq of wildtype mice PBMC
SAMC2918968	RNA-Seq of wildtype mice PBMC
SAMC2918967	RNA-Seq of wildtype mice PBMC
SAMC2918966	RNA-Seq of wildtype mice PBMC
SAMC2918965	RNA-Seq of wildtype mice PBMC
SAMC2918964	RNA-Seq of wildtype mice PBMC
SAMC2918963	RNA-Seq of wildtype mice PBMC
SAMC2918962	RNA-Seq of wildtype mice PBMC
GSA (1)	-
CRA011864	Comprehensive immune profile changes to human interferon stimulation in normal and HBV-infected conditions in a humanized mouse