Ribavirin attenuates the respiratory immune responses to influenza viral infection in mice

Shang-Hui Liao; Yun Li; Yan-Ni Lai; Ni Liu; Feng-Xue Zhang; Pei-Ping Xu

doi:10.1007/s00705-017-3291-7

Ribavirin attenuates the respiratory immune responses to influenza viral infection in mice

Arch Virol. 2017 Jun;162(6):1661-1669. doi: 10.1007/s00705-017-3291-7. Epub 2017 Feb 27.

Authors

Shang-Hui Liao¹, Yun Li¹, Yan-Ni Lai¹, Ni Liu¹, Feng-Xue Zhang¹, Pei-Ping Xu²

Affiliations

¹ Institute of Tropical Medicine, Guangzhou University of Chinese Medicine, 12 Jichang Rd., San Yuanli St., Bai Yun Dist., Guangzhou, 510405, Guangdong, People's Republic of China.
² Institute of Tropical Medicine, Guangzhou University of Chinese Medicine, 12 Jichang Rd., San Yuanli St., Bai Yun Dist., Guangzhou, 510405, Guangdong, People's Republic of China. xupeiping@gzucm.edu.cn.

PMID: 28243801
DOI: 10.1007/s00705-017-3291-7

Abstract

Ribavirin is a broad-spectrum antiviral agent that is used against RNA and DNA viruses and has been reported to inhibit infection by influenza A and B virus in vitro and in vivo. Studies have shown that ribavirin can lower convalescent antibody titers in young children hospitalized with influenza. Here, we report that ribavirin administration in juvenile mice significantly attenuated respiratory immune responses, production of total IgA and hemagglutinin (HA)-specific secretory IgA responses on the mucosal surface. In contrast, systemic IgG and IgA responses were not affected. Ribavirin significantly suppressed toll-like receptor 2 and 4 expression in the lung and decreased the level of IL-1β, IL-6, TNF-α, and IFN-γ in lung tissues of mice infected with influenza virus. Our findings suggest ribavirin appears to be able to inhibit viral replication and, as a result, TLR and cytokine expression are not up-regulated, attenuating inflammation as well as the respiratory tract's immune response.

MeSH terms

Animals
Antiviral Agents / administration & dosage*
Female
Immunoglobulin A / blood
Immunoglobulin A / immunology
Immunoglobulin G / blood
Influenza A Virus, H1N1 Subtype / drug effects*
Influenza A Virus, H1N1 Subtype / immunology
Influenza A Virus, H1N1 Subtype / physiology
Interferon-gamma / genetics
Interleukin-1beta / genetics
Interleukin-6 / genetics
Lung / immunology
Lung / virology
Mice
Orthomyxoviridae Infections / drug therapy*
Orthomyxoviridae Infections / immunology*
Respiratory System / drug effects*
Respiratory System / immunology
Ribavirin / administration & dosage*
Toll-Like Receptor 2 / drug effects
Toll-Like Receptor 2 / genetics
Toll-Like Receptor 4 / drug effects
Toll-Like Receptor 4 / genetics
Tumor Necrosis Factor-alpha / genetics
Virus Replication / drug effects*

Substances

Antiviral Agents
Immunoglobulin A
Immunoglobulin G
Interleukin-1beta
Interleukin-6
Tlr2 protein, mouse
Tlr4 protein, mouse
Toll-Like Receptor 2
Toll-Like Receptor 4
Tumor Necrosis Factor-alpha
interleukin-6, mouse
Ribavirin
Interferon-gamma