Mx1 GTPase accumulates in distinct nuclear domains and inhibits influenza A virus in cells that lack promyelocytic leukaemia protein nuclear bodies Journal Article
| Authors: | Engelhardt, O. G.; Sirma, H.; Pandolfi, P. P.; Haller, O. |
| Article Title: | Mx1 GTPase accumulates in distinct nuclear domains and inhibits influenza A virus in cells that lack promyelocytic leukaemia protein nuclear bodies |
| Abstract: | The interferon-induced murine Mx1 GTPase is a nuclear protein. It specifically inhibits influenza A viruses at the step of primary transcription, a process known to occur in the nucleus of infected cells. However, the exact mechanism of inhibition is still poorly understood. The Mx1 GTPase has previously been shown to accumulate in distinct nuclear dots that are spatially associated with promyelocytic leukaemia protein (PML) nuclear bodies (NBs), but the significance of this association is not known. Here it is reported that, in cells lacking PML and, as a consequence, PML NBs, Mx1 still formed nuclear dots. These dots were indistinguishable from the dots observed in wild-type cells, indicating that intact PML NBs are not required for Mx1 dot formation. Furthermore, Mx1 retained its antiviral activity against influenza A virus in these PML-deficient cells, which were fully permissive for influenza A virus. Nuclear Mx proteins from other species showed a similar subnuclear distribution. This was also the case for the human MxA GTPase when this otherwise cytoplasmic protein was translocated into the nucleus by virtue of a foreign nuclear localization signal. Human MxA and mouse Mx1 do not interact or form heterooligomers. Yet, they co-localized to a large degree when co-expressed in the nucleus. Taken together, these findings suggest that Mx1 dots represent distinct nuclear domains ('Mx nuclear domains') that are frequently associated with, but functionally independent of, PML NBs. © 2004 SGM. |
| Keywords: | protein expression; unclassified drug; gene translocation; human cell; nonhuman; protein function; protein localization; protein analysis; animal cell; mouse; animal; animals; mice; nuclear protein; protein protein interaction; neoplasm proteins; gtp-binding proteins; transcription factor; wild type; physiology; transcription factors; nuclear proteins; growth, development and aging; chemistry; tumor suppressor proteins; tumor protein; murinae; antivirus agent; cell nucleus; tumor suppressor protein; guanine nucleotide binding protein; nuclear localization signal; influenza virus a; antiviral activity; virus protein; antiviral agents; promyelocytic leukemia protein; guanosine triphosphatase; virus inhibition; myxovirus resistance protein a; cytoplasm protein; pml protein, mouse; influenza a virus; virus transcription; human; priority journal; article; protein mx1; myxovirus resistance proteins |
| Journal Title: | Journal of General Virology |
| Volume: | 85 |
| Issue: | 8 |
| ISSN: | 0022-1317 |
| Publisher: | Soc General Microbiology |
| Date Published: | 2004-08-01 |
| Start Page: | 2315 |
| End Page: | 2326 |
| Language: | English |
| DOI: | 10.1099/vir.0.79795-0 |
| PROVIDER: | scopus |
| PUBMED: | 15269373 |
| DOI/URL: | |
| Notes: | J. Gen. Virol. -- Cited By (since 1996):29 -- Export Date: 16 June 2014 -- CODEN: JGVIA -- Source: Scopus |
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