title: Post-exposure antiviral treatment of norovirus infections effectively protects against diarrhea and reduces virus shedding in the stool in a mortality mouse model.
abstract: Noroviruses are a leading cause of gastroenteritis across the world in all age groups and are linked to increased hospitalization and mortality in children, the elderly and immunocompromised. The development of specific antiviral treatment for norovirus gastroenteritis is urgently needed. We explored in a mouse model whether an inhibitor of norovirus replication could be used therapeutically post murine norovirus (MNV)-infection of mice. Using the MNV, we previously discovered that the viral polymerase inhibitor 2'-C-methylcytidine (2CMC) is able to protect against diarrhea and mortality in mice when used prophylactically and to block the transmission of MNV between mice. Here, we investigated whether 2CMC could be used therapeutically, starting treatment between 12 h and 3 days post-infection with 2CMC. Post-exposure treatment of MNV-infected mice with 2CMC was efficient up to 2 days after infection, preventing norovirus-induced diarrhea, delaying and reducing MNV shedding in stool of treated mice. Rehydration of 2CMC-treated animals did not result in a further improvement of the disease evolution compared to antiviral treatment only. The presence of MNV antigens and inflammation in the small intestine of infected mice inversely correlated with the effectiveness of delayed antiviral treatment. Anti-MNV IgGs were detected in re-challenged mice 10 weeks after the first contact, these protected the mice from re-infection. We here demonstrate the benefit of antiviral treatment in ongoing norovirus infections.
authors.affiliation: KU Leuven, University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven, Belgium.
authors.forename: Joana
authors.initials: J
authors.lastname: Rocha-Pereira
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Abimbola O
authors.initials: AO
authors.lastname: Kolawole
authors.affiliation: KU Leuven - University of Leuven, Department of Imaging & Pathology, Translational Cell & Tissue Research, Leuven, Belgium.
authors.forename: Eric
authors.initials: E
authors.lastname: Verbeken
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Christiane E
authors.initials: CE
authors.lastname: Wobus
authors.affiliation: KU Leuven, University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven, Belgium. Electronic address: johan.neyts@kuleuven.be.
authors.forename: Johan
authors.initials: J
authors.lastname: Neyts
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D000956:Antigens, Viral; D000998:Antiviral Agents / Q000494:pharmacology*; D017250:Caliciviridae Infections / Q000188:drug therapy / Q000276:immunology / Q000401:mortality / Q000821:virology*; D003967:Diarrhea / Q000188:drug therapy / Q000276:immunology / Q000401:mortality / Q000821:virology*; D004195:Disease Models, Animal; D005243:Feces / Q000821:virology*; D005440:Fluid Therapy; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D051379:Mice; D029322:Norovirus / Q000187:drug effects* / Q000502:physiology*; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects; D017201:Virus Shedding / Q000187:drug effects*
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D000998:Antiviral Agents; D007074:Immunoglobulin G
keywords: Antiviral drugs; Control and prevention; Diarrhea; Mouse model; Outbreak