Abstract Title
Synergistic Effect of Magnesium and Bile Acid GCDCA on Antibody Escape by Human Norovirus
Presenter
Stefan Taube, University of Lübeck
Co-Author(s)
Maryna Chaika1, Lorena Rudolph2, Alvaro Mallagaray de Benito2, Sandra Niendorf3, Carmen Mirabelli1,4, Christiane Wobus4, Stefan Taube1
1Institute of Virology and Cell Biology, University of Luebeck, Germany
2Institute for Chemistry and Metabolomics, University of Luebeck, Germany
3Unit Gastroenteritis and Hepatitis Viruses and Enteroviruses, Department of Infectious Diseases, Robert Koch Institute, Berlin, Germany
4Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, USA
Abstract Category
Structure & Pathogenesis
Abstract
Human noroviruses (HNoVs) are single-stranded RNA viruses responsible for many cases of acute gastroenteritis worldwide. In vitro studies have been challenging, but human intestinal enteroids (HIEs), derived from stem cells, now allow detailed analysis of viral entry. HNoV infection depends on histo-blood group antigens (HBGAs); however, the influence of environmental factors such as divalent cations and bile acids like glycochenodeoxycholic acid (GCDCA) remains poorly understood.
This study investigated the effects of magnesium and GCDCA on HNoV infection and escape from the neutralizing antibody A1431 in differentiated 3D HIE cultures, using three GII.4 stool isolates, two Den Haag-like and one Yerseke-like. Infections were performed with 50 mM magnesium chloride, 500 uM GCDCA, or both. Viral replication was quantified by RT-qPCR at 2 hours and 2 days post-infection.
Magnesium modestly increased infectivity of Den Haag #1 (3-fold) and Yerseke (5-fold), while GCDCA alone had no effect. Notably, the combination of magnesium and GCDCA enhanced infection significantly—15-fold for Den Haag #1 and 10-fold for Yerseke. Den Haag #2 remained unresponsive to all treatments. Sequence analysis linked this phenotype to an epitope spanning residues 499–505, containing a newly identified magnesium-binding epitope, involving histidines at positions 500 and 504 in Den Haag #1. The combination treatment also enabled antibody escape in Den Haag #1, but not in the other two isolates.
These findings demonstrate that magnesium and GCDCA can synergistically promote HNoV infection and antibody escape in a strain-specific manner, highlighting the importance of gut microenvironmental factors in viral pathogenesis.
This study investigated the effects of magnesium and GCDCA on HNoV infection and escape from the neutralizing antibody A1431 in differentiated 3D HIE cultures, using three GII.4 stool isolates, two Den Haag-like and one Yerseke-like. Infections were performed with 50 mM magnesium chloride, 500 uM GCDCA, or both. Viral replication was quantified by RT-qPCR at 2 hours and 2 days post-infection.
Magnesium modestly increased infectivity of Den Haag #1 (3-fold) and Yerseke (5-fold), while GCDCA alone had no effect. Notably, the combination of magnesium and GCDCA enhanced infection significantly—15-fold for Den Haag #1 and 10-fold for Yerseke. Den Haag #2 remained unresponsive to all treatments. Sequence analysis linked this phenotype to an epitope spanning residues 499–505, containing a newly identified magnesium-binding epitope, involving histidines at positions 500 and 504 in Den Haag #1. The combination treatment also enabled antibody escape in Den Haag #1, but not in the other two isolates.
These findings demonstrate that magnesium and GCDCA can synergistically promote HNoV infection and antibody escape in a strain-specific manner, highlighting the importance of gut microenvironmental factors in viral pathogenesis.