Abstract
The Mx2 protein of rats is a cytoplasmic GTPase that protects cells against vesicular stomatitis virus but not against influenza virus. Since vesicular stomatitis virus replicates in the cytoplasm and influenza virus replicates in the nucleus, it was possible that the antiviral specificity of rat Mx2 protein was determined solely by the protein's subcellular localization. Here, we found that, indeed, rat Mx2 protein lost its anti-vesicular stomatitis virus activity and gained anti-influenza virus activity when it was directed to the nucleus by way of a foreign nuclear-transport signal appended to its amino terminus. These data show that rat Mx2 protein possesses an antiviral activity that is revealed only when the protein is shuttled to the nucleus.
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Selected References
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- Arnheiter H., Meier E. Mx proteins: antiviral proteins by chance or by necessity? New Biol. 1990 Oct;2(10):851–857. [PubMed] [Google Scholar]
- Arnheiter H., Skuntz S., Noteborn M., Chang S., Meier E. Transgenic mice with intracellular immunity to influenza virus. Cell. 1990 Jul 13;62(1):51–61. doi: 10.1016/0092-8674(90)90239-b. [DOI] [PubMed] [Google Scholar]
- Bourne H. R., Sanders D. A., McCormick F. The GTPase superfamily: conserved structure and molecular mechanism. Nature. 1991 Jan 10;349(6305):117–127. doi: 10.1038/349117a0. [DOI] [PubMed] [Google Scholar]
- Dreiding P., Staeheli P., Haller O. Interferon-induced protein Mx accumulates in nuclei of mouse cells expressing resistance to influenza viruses. Virology. 1985 Jan 15;140(1):192–196. doi: 10.1016/0042-6822(85)90460-x. [DOI] [PubMed] [Google Scholar]
- Feldherr C. M., Akin D. The permeability of the nuclear envelope in dividing and nondividing cell cultures. J Cell Biol. 1990 Jul;111(1):1–8. doi: 10.1083/jcb.111.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Horisberger M. A. Interferon-induced human protein MxA is a GTPase which binds transiently to cellular proteins. J Virol. 1992 Aug;66(8):4705–4709. doi: 10.1128/jvi.66.8.4705-4709.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kalderon D., Roberts B. L., Richardson W. D., Smith A. E. A short amino acid sequence able to specify nuclear location. Cell. 1984 Dec;39(3 Pt 2):499–509. doi: 10.1016/0092-8674(84)90457-4. [DOI] [PubMed] [Google Scholar]
- Krug R. M., Shaw M., Broni B., Shapiro G., Haller O. Inhibition of influenza viral mRNA synthesis in cells expressing the interferon-induced Mx gene product. J Virol. 1985 Oct;56(1):201–206. doi: 10.1128/jvi.56.1.201-206.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Meier E., Fäh J., Grob M. S., End R., Staeheli P., Haller O. A family of interferon-induced Mx-related mRNAs encodes cytoplasmic and nuclear proteins in rat cells. J Virol. 1988 Jul;62(7):2386–2393. doi: 10.1128/jvi.62.7.2386-2393.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Meier E., Kunz G., Haller O., Arnheiter H. Activity of rat Mx proteins against a rhabdovirus. J Virol. 1990 Dec;64(12):6263–6269. doi: 10.1128/jvi.64.12.6263-6269.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nakayama M., Nagata K., Kato A., Ishihama A. Interferon-inducible mouse Mx1 protein that confers resistance to influenza virus is GTPase. J Biol Chem. 1991 Nov 15;266(32):21404–21408. [PubMed] [Google Scholar]
- Noteborn M., Arnheiter H., Richter-Mann L., Browning H., Weissmann C. Transport of the murine Mx protein into the nucleus is dependent on a basic carboxy-terminal sequence. J Interferon Res. 1987 Oct;7(5):657–669. doi: 10.1089/jir.1987.7.657. [DOI] [PubMed] [Google Scholar]
- Parker B. A., Stark G. R. Regulation of simian virus 40 transcription: sensitive analysis of the RNA species present early in infections by virus or viral DNA. J Virol. 1979 Aug;31(2):360–369. doi: 10.1128/jvi.31.2.360-369.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pavlovic J., Haller O., Staeheli P. Human and mouse Mx proteins inhibit different steps of the influenza virus multiplication cycle. J Virol. 1992 Apr;66(4):2564–2569. doi: 10.1128/jvi.66.4.2564-2569.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pavlovic J., Zürcher T., Haller O., Staeheli P. Resistance to influenza virus and vesicular stomatitis virus conferred by expression of human MxA protein. J Virol. 1990 Jul;64(7):3370–3375. doi: 10.1128/jvi.64.7.3370-3375.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Staeheli P., Grob R., Meier E., Sutcliffe J. G., Haller O. Influenza virus-susceptible mice carry Mx genes with a large deletion or a nonsense mutation. Mol Cell Biol. 1988 Oct;8(10):4518–4523. doi: 10.1128/mcb.8.10.4518. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Staeheli P., Haller O., Boll W., Lindenmann J., Weissmann C. Mx protein: constitutive expression in 3T3 cells transformed with cloned Mx cDNA confers selective resistance to influenza virus. Cell. 1986 Jan 17;44(1):147–158. doi: 10.1016/0092-8674(86)90493-9. [DOI] [PubMed] [Google Scholar]
- Staeheli P., Pavlovic J. Inhibition of vesicular stomatitis virus mRNA synthesis by human MxA protein. J Virol. 1991 Aug;65(8):4498–4501. doi: 10.1128/jvi.65.8.4498-4501.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zürcher T., Pavlovic J., Staeheli P. Mechanism of human MxA protein action: variants with changed antiviral properties. EMBO J. 1992 Apr;11(4):1657–1661. doi: 10.1002/j.1460-2075.1992.tb05212.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zürcher T., Pavlovic J., Staeheli P. Mouse Mx2 protein inhibits vesicular stomatitis virus but not influenza virus. Virology. 1992 Apr;187(2):796–800. doi: 10.1016/0042-6822(92)90481-4. [DOI] [PubMed] [Google Scholar]
- Zürcher T., Pavlovic J., Staeheli P. Nuclear localization of mouse Mx1 protein is necessary for inhibition of influenza virus. J Virol. 1992 Aug;66(8):5059–5066. doi: 10.1128/jvi.66.8.5059-5066.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]