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Activity of rat Mx proteins against a rhabdovirus
1Laboratory of Viral and Molecular Pathogenesis, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892.
Abstract:
Upon stimulation with alpha/beta interferon, rat cells synthesize three Mx proteins. Sequence analysis of corresponding cDNAs reveals that these three proteins are derived from three distinct genes. One of the rat cDNAs is termed Mx1 because it is most closely related to the mouse Mx1 cDNA and because it codes for a nuclear protein that, like the mouse Mx1 protein, inhibits influenza virus growth. However, this protein differs from mouse Mx1 protein, in that it also inhibits vesicular stomatitis virus (VSV), a rhabdovirus. A second rat cDNA is more closely related to the mouse Mx2 cDNA and directs the synthesis of a cytoplasmic protein that inhibits VSV but not influenza virus. The third rat cDNA codes for a cytoplasmic protein that differs from the second one in only eight positions and has no detectable activity against either virus. These results indicate that rat Mx proteins have antiviral specificities not anticipated from the analysis of the murine Mx1 protein.
Insights
Rat cells produce three interferon-induced Mx proteins from distinct genes. These proteins exhibit unique antiviral activities against influenza and vesicular stomatitis virus (VSV), expanding known Mx protein functions.
Area of Science:
- Molecular Biology
- Virology
- Immunology
Background:
- Interferons (IFNs) are crucial cytokines in antiviral defense.
- Mx proteins are key mediators of IFN-induced antiviral states.
- Understanding Mx protein diversity and function is vital for antiviral strategies.
Purpose of the Study:
- To characterize novel rat Mx proteins induced by interferon.
- To determine the antiviral specificities of these rat Mx proteins.
- To compare rat Mx protein functions with known murine Mx proteins.
Main Methods:
- cDNA sequencing of interferon-stimulated rat cells.
- Expression and analysis of synthesized Mx proteins.
- Antiviral assays against influenza virus and vesicular stomatitis virus (VSV).
Main Results:
- Three distinct rat Mx proteins (Mx1, Mx2-like, and a variant) were identified from separate genes.
- Rat Mx1 protein, a nuclear protein, inhibited both influenza virus and VSV.
- A cytoplasmic rat Mx protein (Mx2-like) inhibited VSV but not influenza virus.
- A third variant protein showed no detectable antiviral activity.
Conclusions:
- Rat Mx proteins possess distinct antiviral specificities compared to murine Mx1.
- The functional diversity of Mx proteins is broader than previously understood.
- Rat Mx proteins offer new insights into interferon-mediated antiviral immunity.