Discovery of Novel Host Molecular Factors Underlying HBV/HCV Infection

Xubo Huang; Joseph T Glessner; Jinxia Huang; Desheng Zhou; Michael E March; Hongna Wang; Qianghua Xia; Hakon Hakonarson; Jin Li

doi:10.3389/fcell.2021.690882

Discovery of Novel Host Molecular Factors Underlying HBV/HCV Infection

Front Cell Dev Biol. 2021 Aug 12:9:690882. doi: 10.3389/fcell.2021.690882. eCollection 2021.

Authors

Xubo Huang^{1

2}, Joseph T Glessner³, Jinxia Huang^{1

2}, Desheng Zhou^{1

2}, Michael E March³, Hongna Wang^{1

2}, Qianghua Xia^{1

2}, Hakon Hakonarson^{3

4

5}, Jin Li^{1

2}

Affiliations

¹ Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China.
² Key Laboratory for Cell Homeostasis and Cancer Research of Guangdong Higher Education Institutes, Guangzhou Medical University, Guangzhou, China.
³ Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA, United States.
⁴ Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
⁵ Division of Human Genetics and Division of Pulmonary Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, United States.

Abstract

Hepatitis is an inflammatory condition of the liver, which is frequently caused by the infection of hepatitis B virus (HBV) or hepatitis C virus (HCV). Hepatitis can lead to the development of chronic complications including cancer, making it a major public health burden. Co-infection of HBV and HCV can result in faster disease progression. Therefore, it is important to identify shared genetic susceptibility loci for HBV and HCV infection to further understand the underlying mechanism. Through a meta-analysis based on genome-wide association summary statistics of HBV and HCV infection, we found one novel locus in the Asian population and two novel loci in the European population. By functional annotation based on multi-omics data, we identified the likely target genes at each novel locus, such as HMGB1 and ATF3, which play a critical role in autophagy and immune response to virus. By re-analyzing a microarray dataset from Hmgb1^-/- mice and RNA-seq data from mouse liver tissue overexpressing ATF3, we found that differential expression of autophagy and immune and metabolic gene pathways underlie these conditions. Our study reveals novel common susceptibility loci to HBV and HCV infection, supporting their role in linking autophagy signaling and immune response.

Keywords: autophagy; genome-wide association study; hepatitis infection; immune response to virus; microarray.