Human Receptor for Measles Virus (CD46) Enhances Nitric Oxide Production and Restricts Virus Replication in Mouse Macrophages by Modulating Production of Alpha/Beta Interferon
AUTOR(ES)
Katayama, Yuko
FONTE
American Society for Microbiology
RESUMO
Complement regulatory protein CD46 is a human cell receptor for measles virus (MV). In this study, we investigated why mouse macrophages expressing human CD46 restricted MV replication and produced higher levels of nitric oxide (NO) in response to MV and gamma interferon (IFN-γ). Treatment of MV-infected CD46-expressing mouse macrophages with antibodies against IFN-α/β blocked NO production. Antibodies against IFN-α/β also inhibited the augmenting effect of MV on IFN-γ-induced NO production in CD46-expressing mouse macrophages. These antibodies did not affect NO production induced by IFN-γ alone. These data suggest that MV enhances NO production in CD46-expressing mouse macrophages through action of IFN-α/β. Mouse macrophages expressing a human CD46 mutant lacking the cytoplasmic domains were highly susceptible to MV. These cells produced much lower levels of NO and IFN-α/β upon infection by MV, suggesting the CD46 cytoplasmic domains enhanced IFN-α/β production. When mouse macrophages expressing tailless human CD46 were exposed to culture medium from MV-infected mouse macrophages expressing intact human CD46, viral protein synthesis and development of cytopathic effects were suppressed. Pretreating the added culture medium with antibodies against IFN-α/β abrogated these antiviral effects. Taken together, these findings suggest that expression of human CD46 in mouse macrophages enhances production of IFN-α/β in response to MV infection, and IFN-α/β synergizes with IFN-γ to enhance NO production and restrict viral protein synthesis and virus replication. This novel function of human CD46 in mouse macrophages requires the CD46 cytoplasmic domains.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=111459Documentos Relacionados
- Human CD46 Enhances Nitric Oxide Production in Mouse Macrophages in Response to Measles Virus Infection in the Presence of Gamma Interferon: Dependence on the CD46 Cytoplasmic Domains
- Inhibitory Activity of Constitutive Nitric Oxide on the Expression of Alpha/Beta Interferon Genes in Murine Peritoneal Macrophages
- Evasion of Host Defenses by Measles Virus: Wild-Type Measles Virus Infection Interferes with Induction of Alpha/Beta Interferon Production
- Role of interferon alpha/beta receptor chain 1 in the structure and transmembrane signaling of the interferon alpha/beta receptor complex.
- Human membrane cofactor protein (CD46) acts as a cellular receptor for measles virus.