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Interferon-inducible Mx proteins in fish
J C Leong1, G D Trobridge, C H Kim
1Department of Microbiology, Oregon State University, Corvallis, USA. leongj@orst.edu
Abstract:
Mx proteins are members of a family of interferon-inducible genes expressed when cells are treated with double-stranded RNA or virus infection. These proteins are important components of the antiviral response and form the first line of the body's defense against virus infections. The exact mechanism of action for these proteins has not been discovered, but mice missing the Mx genes are extremely sensitive to influenza virus infection. Mammals have between two and three Mx genes whose functions may vary with regard to the inhibition of a specific virus, cellular localization, and activity. The cDNA of three rainbow trout Mx proteins has been cloned and a comparison of their sequences with that of avian and mammalian species reveals striking conservation of domains. They all maintain the tripartite ATP/GTP binding domain and the dynamin family signature in the amino terminal half of the protein. In the carboxyl terminal half of the Mx proteins are the localization signals and the leucine zipper motifs which account for the trimerization of Mx in the cell. Like the rat and human Mx proteins, the different trout Mx proteins exhibit distinctly different immunohistochemical staining patterns in cells transfected with plasmids expressing RBTMx1, RBTMx2, or RBTMx3. To date, the antiviral function of the trout Mx proteins has not been satisfactorily established.
Insights
Mx proteins are crucial for antiviral defense. Rainbow trout Mx proteins share conserved domains with mammals, but their specific antiviral functions require further investigation.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- Mx proteins are interferon-inducible, playing a key role in the innate antiviral immune response.
- Mammalian Mx proteins exhibit variations in viral inhibition, cellular localization, and activity.
- Mice lacking Mx genes show heightened susceptibility to influenza virus infections.
Purpose of the Study:
- To clone and characterize three rainbow trout Mx proteins (RBTMx1, RBTMx2, RBTMx3).
- To compare the sequence conservation of trout Mx proteins with avian and mammalian counterparts.
- To investigate the cellular localization and potential antiviral functions of trout Mx proteins.
Main Methods:
- Cloning of rainbow trout Mx protein cDNAs.
- Sequence analysis and comparison with avian and mammalian Mx proteins.
- Immunohistochemical staining of transfected cells to determine protein localization.
Main Results:
- Three rainbow trout Mx protein cDNAs were successfully cloned.
- Striking conservation of ATP/GTP binding domains and dynamin family signatures was observed between trout, avian, and mammalian Mx proteins.
- Distinct immunohistochemical staining patterns were observed for RBTMx1, RBTMx2, and RBTMx3 in transfected cells, similar to rat and human Mx proteins.
Conclusions:
- Rainbow trout Mx proteins share conserved structural domains with Mx proteins from other vertebrate species.
- The distinct cellular localization patterns suggest specialized roles for different trout Mx proteins.
- The specific antiviral functions of rainbow trout Mx proteins remain to be definitively established.