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http://purl.uniprot.org/citations/36932045http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/36932045http://www.w3.org/2000/01/rdf-schema#comment"

Background

Alpha kinase 1 (ALPK1) agonist has recently been reported to demonstrate anti-hepatitis B virus (HBV) efficacy via activating NF-κB signaling, which is crucial for maximizing interferon (IFN) responses. Here, we investigated the impact of ALPK1 on HBV replication and explored ALPK1 variants for predicting the response to pegylated IFN-α (PegIFN-α) treatment.

Methods

The potential anti-HBV effect of ALPK1 was evaluated in HBV-integrated and HBV-infected hepatoma cells. The potentially functional genetic variants of ALPK1 were screened out, and their correlations with PegIFN-α treatment response were assessed in 945 hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B (CHB).

Results

We revealed that ALPK1 inhibited HBV replication in hepatocytes via activating the JAK-STAT pathway. ALPK1 overexpression improved the anti-HBV effect of IFN-α in cell models. A missense variant, rs35389530 (P660L), of ALPK1 was strongly associated with combined response (CR; namely, HBeAg seroconversion and HBV DNA level <3.3log10 IU/mL) to PegIFN-α treatment in patients with CHB (P = 2.12 × 10-6). Moreover, a polygenic score integrating ALPK1_rs35389530 and 2 additional genetic variants was further significantly associated with CR (Ptrend = 9.28 × 10-7), hepatitis B surface antigen (HBsAg) level (Ptrend = .0002), and HBsAg loss (Ptrend = .025).

Conclusions

The anti-HBV effects of ALPK1 through activating JAK-STAT pathway provides a new perspective for CHB therapy. ALPK1_rs35389530 and polygenic score are potential biomarkers to predict PegIFN-α treatment response and may be used for optimizing CHB treatment."xsd:string
http://purl.uniprot.org/citations/36932045http://purl.org/dc/terms/identifier"doi:10.1093/infdis/jiad065"xsd:string
http://purl.uniprot.org/citations/36932045http://purl.uniprot.org/core/author"Chen J."xsd:string
http://purl.uniprot.org/citations/36932045http://purl.uniprot.org/core/author"Chen H."xsd:string
http://purl.uniprot.org/citations/36932045http://purl.uniprot.org/core/author"Lou S."xsd:string
http://purl.uniprot.org/citations/36932045http://purl.uniprot.org/core/author"Wang J."xsd:string
http://purl.uniprot.org/citations/36932045http://purl.uniprot.org/core/author"Zhang B."xsd:string
http://purl.uniprot.org/citations/36932045http://purl.uniprot.org/core/author"Zhou B."xsd:string
http://purl.uniprot.org/citations/36932045http://purl.uniprot.org/core/author"Hou J."xsd:string
http://purl.uniprot.org/citations/36932045http://purl.uniprot.org/core/author"Xie H."xsd:string
http://purl.uniprot.org/citations/36932045http://purl.uniprot.org/core/author"Jiang D.K."xsd:string
http://purl.uniprot.org/citations/36932045http://purl.uniprot.org/core/date"2023"xsd:gYear
http://purl.uniprot.org/citations/36932045http://purl.uniprot.org/core/name"J Infect Dis"xsd:string
http://purl.uniprot.org/citations/36932045http://purl.uniprot.org/core/pages"694-703"xsd:string
http://purl.uniprot.org/citations/36932045http://purl.uniprot.org/core/title"The Role of ALPK1 in Inhibiting Hepatitis B Virus Replication Facilitates the Identification of ALPK1 P660L Variant for Predicting Response to Pegylated Interferon alpha Therapy."xsd:string
http://purl.uniprot.org/citations/36932045http://purl.uniprot.org/core/volume"228"xsd:string
http://purl.uniprot.org/citations/36932045http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/36932045
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