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IPS-1 polymorphisms in regulating interferon response in HBV infection.

Kehui Liu^1,2, Liwen Chen¹, Gangde Zhao²

¹Department of Infectious Diseases, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine.

Bioscience Trends

|April 2, 2019

Summary

Single nucleotide polymorphisms (SNPs) in Interferon β promoter stimulator 1 (IPS-1) affect hepatitis B virus (HBV) clearance. Specific IPS-1 SNPs (rs17857295, rs7262903) enhance viral clearance by boosting interferon-beta production.

Keywords:

IPS-1 chronic HBV infection hepatitis B virus interferon response single nucleotide polymorphism

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Stem Cell-Derived Viral Ag-Specific T Lymphocytes Suppress HBV Replication in Mice

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Published on: September 25, 2019

Area of Science:

Immunology
Virology
Genetics

Background:

Single nucleotide polymorphisms (SNPs) are known to influence treatment outcomes in chronic hepatitis B (CHB) patients.
Interferon β promoter stimulator 1 (IPS-1) plays a crucial role in regulating interferon (IFN)-mediated viral clearance during hepatitis B virus (HBV) infection.

Purpose of the Study:

To investigate the impact of different IPS-1 single nucleotide polymorphism (SNP) genotypes on IPS-1 and interferon (IFN) production in HBV-infected cells.
To determine the association between specific IPS-1 SNPs and the efficiency of viral clearance in chronic hepatitis B.

Main Methods:

HepG2 and HepG2.2.15 cell lines were transfected with expression vectors encoding wild-type IPS-1 and IPS-1 variants (rs17857295, rs7262903, rs7269320).
Quantification of IPS-1 and IFN-β production was performed in the transfected cells to assess functional differences between genotypes.

Main Results:

Transfection with IPS-1 rs17857295 or rs7262903 SNPs resulted in significantly lower IPS-1 levels but markedly higher IFN-β levels in HepG2.2.15 cells compared to wild-type.
IPS-1 rs7269320 SNP transfection also led to reduced IPS-1, but did not significantly alter IFN-β levels compared to wild-type.
IFN-β expression was significantly elevated in rs17857295-transfected HepG2.2.15 cells compared to untransfected HepG2 cells.

Conclusions:

The IPS-1 rs17857295 and rs7262903 SNP genotypes are associated with stronger host HBV viral clearance, likely due to enhanced inducible IFN-β production.
Reduced IFN-β production in patients with IPS-1 rs7269320 SNP or wild-type genotypes may contribute to the persistence of chronic HBV infection.