An ectromelia virus profilin homolog interacts with cellular tropomyosin and viral A-type inclusion protein

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dc.contributor.authorButler-Cole, Christine
dc.contributor.authorWagner, Mary J
dc.contributor.authorDa Silva, Melissa
dc.contributor.authorBrown, Gordon D
dc.contributor.authorBurke, Robert D
dc.contributor.authorUpton, Chris
dc.date.accessioned2014-07-15T23:47:31Z
dc.date.available2014-07-15T23:47:31Z
dc.date.copyright2007en_US
dc.date.issued2007-07-24
dc.descriptionBioMed Centralen_US
dc.description.abstractBackground: Profilins are critical to cytoskeletal dynamics in eukaryotes; however, little is known about their viral counterparts. In this study, a poxviral profilin homolog, ectromelia virus strain Moscow gene 141 (ECTV-PH), was investigated by a variety of experimental and bioinformatics techniques to characterize its interactions with cellular and viral proteins. Results: Profilin-like proteins are encoded by all orthopoxviruses sequenced to date, and share over 90% amino acid (aa) identity. Sequence comparisons show highest similarity to mammalian type 1 profilins; however, a conserved 3 aa deletion in mammalian type 3 and poxviral profilins suggests that these homologs may be more closely related. Structural analysis shows that ECTVPH can be successfully modelled onto both the profilin 1 crystal structure and profilin 3 homology model, though few of the surface residues thought to be required for binding actin, poly(L-proline), and PIP2 are conserved. Immunoprecipitation and mass spectrometry identified two proteins that interact with ECTV-PH within infected cells: alpha-tropomyosin, a 38 kDa cellular actin-binding protein, and the 84 kDa product of vaccinia virus strain Western Reserve (VACV-WR) 148, which is the truncated VACV counterpart of the orthopoxvirus A-type inclusion (ATI) protein. Western and far-western blots demonstrated that the interaction with alpha-tropomyosin is direct, and immunofluorescence experiments suggest that ECTV-PH and alpha-tropomyosin may colocalize to structures that resemble actin tails and cellular protrusions. Sequence comparisons of the poxviral ATI proteins show that although full-length orthologs are only present in cowpox and ectromelia viruses, an ~ 700 aa truncated ATI protein is conserved in over 90% of sequenced orthopoxviruses. Immunofluorescence studies indicate that ECTV-PH localizes to cytoplasmic inclusion bodies formed by both truncated and full-length versions of the viral ATI protein. Furthermore, colocalization of ECTV-PH and truncated ATI protein to protrusions from the cell surface was observed. Conclusion: These results suggest a role for ECTV-PH in intracellular transport of viral proteins or intercellular spread of the virus. Broader implications include better understanding of the virushost relationship and mechanisms by which cells organize and control the actin cytoskeleton.en_US
dc.description.reviewstatusRevieweden_US
dc.description.scholarlevelFacultyen_US
dc.description.sponsorshipMolecular graphics images were produced using the UCSF Chimera package from the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco (supported by NIH P41 RR-01081). The project was supported by funding from the Protein Engineering Network Centre of Excellence and NIH/NAID Contract HHSN266200400036C.en_US
dc.identifier.citationButler-Cole C. et al. An ectromelia virus profilin homolog interacts with cellular tropomyosin and viral A-type inclusion protein. Virology Journal 2007, 4 :76en_US
dc.identifier.urihttp://www.virologyj.com/content/4/1/76
dc.identifier.urihttp://dx.doi.org/doi:10.1186/1743-422X-4-76
dc.identifier.urihttp://hdl.handle.net/1828/5458
dc.language.isoenen_US
dc.publisherBioMed Centralen_US
dc.titleAn ectromelia virus profilin homolog interacts with cellular tropomyosin and viral A-type inclusion proteinen_US
dc.typeArticleen_US

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