Interferon-stimulated gene GALNT2 restricts respiratory virus infections
Year: 2025
Type: article
Abstract: The innate immune response involves interferons (IFNs), antiviral cytokines that upregulate numerous IFN-stimulated genes, many of which have uncharacterized functions and mechanisms. Here we performed transcriptomic profiling of lung tissues from wild-type and IFNAR−/− mice infected with SARS-CoV-2 and single-cell RNA sequencing of bronchoalveolar lavage fluid and peripheral blood mononuclear cells from patients with COVID-19. We identified O-GalNAc transferase 2 (GALNT2), an N-acetylgalactosaminyltransferase, as an antiviral IFN-stimulated gene restricting the replication of multiple coronaviruses and influenza A viruses in vitro and in vivo, contributing to viral clearance and reducing disease severity. Mechanistically, GALNT2-dependent O-linked glycosylation may regulate viral glycoprotein proteolytic processing and impair viral growth by blocking virus–cell fusion. In addition, we found that serine residues at 810/813 in the viral spike protein undergo O-glycosylation and function as the primary genetic determinants of sensitivity or evasion towards GALNT2. Human genetic data analysis revealed that individuals with GALNT2 variants that lost antiviral function had elevated risk of hospitalization following SARS-CoV-2 infection. This study establishes GALNT2 as an antiviral factor against some respiratory virus infections. The authors find that O-GalNAc transferase 2 (GALNT2) restricts viral infection, probably through the regulation of the proteolytic processing of viral glycoproteins via its O-linked glycosylation activity, impairing virus–cell fusion.
Source: Nature Microbiology
Authors: Wei Ran, Jinghong Yang, Shi Yu, Qingtao Hu, Yuqi He, Shengjun Wang, Shengjun Wang, Cheng Wei, Jing Sun, Airu Zhu, Fang Li, Lu Zhang, Pengfei Li, Huina Hu, Ruangang Pan, Yanying Yu, Yanqiu Yuan, Lingyu Sun, Yanqun Wang, Zhaoyong Zhang, Zhao Chen, Donglan Liu, Qihong Yan, Dong Wang, Kuai Yu, Yiliang Wang, Jianfen Zhuo, Zhen Zhuang, Hua Tao, Qiuhui Zeng, Kaixin Zhou, Fenghua Chen, Wenxuan Tang, Yuzheng Zhou, Rong Bai, Yonghao Xu, Na Li, Jun Dai, Hongyu Zhao, Jung-Eun Park, Tao Wang, Qiang Ding, Stanley Perlman, Jingxian Zhao, Yang Mao, Shaobo Wang, Shaobo Wang, Jincun Zhao
Institutions: First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, Guangzhou Laboratory, Guangzhou Institute of Respiratory Health, Guangzhou Medical University, Sun Yat-sen University, University of Health and Rehabilitation Sciences, University of Iowa, Tsinghua University, Southern University of Science and Technology, Shenzhen Third People’s Hospital, TCM-Intigrated Cancer Center of Southern Medical University, Southern Medical University, Chungnam National University, ShanghaiTech University
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
OpenAlex ID: W4417269415