Title Chemokine CCL6 Plays Key Role in the Inhibitory Effect of Vitamin A on Norovirus Infection
Author Heetae Lee1*, Giljae Lee2, You‑Hee Cho3, Youngcheon Song1, and GwangPyo Ko2*
Address 1College of Pharmacy, Sahmyook University, Seoul 01795, Republic of Korea, 2Center for Human and Environmental Microbiome, School of Public Health, Seoul National University, Seoul 08826, Republic of Korea, 3Department of Pharmacy, College of Pharmacy, CHA University, Seongnam 13488, Republic of Korea
Bibliography Journal of Microbiology, 61(5),579-587, 2023,
DOI 10.1007/s12275-023-00047-3
Key Words Vitamin A · Norovirus (NoV) · CCL6 · HG23 cell
Abstract Norovirus (NoV) is the most common viral cause of acute gastroenteritis worldwide. Vitamin A has demonstrated the potential to protect against gastrointestinal infections. However, the effects of vitamin A on human norovirus (HuNoV) infections remain poorly understood. This study aimed to investigate how vitamin A administration affects NoV replication. We demonstrated that treatment with retinol or retinoic acid (RA) inhibited NoV replication in vitro based on their effects on HuNoV replicon-bearing cells and murine norovirus-1 (MNV-1) replication in murine cells. MNV replication in vitro showed significant transcriptomic changes, which were partially reversed by retinol treatment. RNAi knockdown of CCL6, a chemokine gene that was downregulated by MNV infection but upregulated by retinol administration, resulted in increased MNV replication in vitro. This suggested a role of CCL6 in the host response to MNV infections. Similar gene expression patterns were observed in the murine intestine after oral administration of RA and/or MNV-1.CW1. CCL6 directly decreased HuNoV replication in HG23 cells, and might indirectly regulate the immune response against NoV infection. Finally, relative replication levels of MNV-1.CW1 and MNV-1.CR6 were significantly increased in CCL6 knockout RAW 264.7 cells. This study is the first to comprehensively profile transcriptomes in response to NoV infection and vitamin A treatment in vitro, and thus may provide new insights into dietary prophylaxis and NoV infections.