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Localization and Importance of the Adenovirus E4orf4 Protein during Lytic Infection
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| Zeitschriftentitel: | Journal of Virology |
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| Personen und Körperschaften: | , , , , , , , |
| In: | Journal of Virology, 83, 2009, 4, S. 1689-1699 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Society for Microbiology
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| Schlagwörter: |
| author_facet |
Miron, Marie-Joëlle Blanchette, Paola Groitl, Peter Dallaire, Frederic Teodoro, Jose G. Li, Suiyang Dobner, Thomas Branton, Philip E. Miron, Marie-Joëlle Blanchette, Paola Groitl, Peter Dallaire, Frederic Teodoro, Jose G. Li, Suiyang Dobner, Thomas Branton, Philip E. |
|---|---|
| author |
Miron, Marie-Joëlle Blanchette, Paola Groitl, Peter Dallaire, Frederic Teodoro, Jose G. Li, Suiyang Dobner, Thomas Branton, Philip E. |
| spellingShingle |
Miron, Marie-Joëlle Blanchette, Paola Groitl, Peter Dallaire, Frederic Teodoro, Jose G. Li, Suiyang Dobner, Thomas Branton, Philip E. Journal of Virology Localization and Importance of the Adenovirus E4orf4 Protein during Lytic Infection Virology Insect Science Immunology Microbiology |
| author_sort |
miron, marie-joëlle |
| spelling |
Miron, Marie-Joëlle Blanchette, Paola Groitl, Peter Dallaire, Frederic Teodoro, Jose G. Li, Suiyang Dobner, Thomas Branton, Philip E. 0022-538X 1098-5514 American Society for Microbiology Virology Insect Science Immunology Microbiology http://dx.doi.org/10.1128/jvi.01703-08 <jats:title>ABSTRACT</jats:title> <jats:p> The human adenovirus type 5 (Ad5) E4orf4 product has been studied extensively although in most cases as expressed from vectors in the absence of other viral products. Thus, relatively little is known about its role in the context of an adenovirus infection. Although considerable earlier work had indicated that the E4orf4 protein is not essential for replication, a recent study using <jats:italic>dl</jats:italic> 359, an Ad5 mutant believed to produce a nonfunctional E4orf4 protein, suggested that E4orf4 is essential for virus growth in primary small-airway epithelial cells (C. O'Shea, et al., EMBO J. 24:1211-1221, 2005). Hence, to examine further the role of E4orf4 during virus infection, we generated for the first time a set of E4orf4 virus mutants in a common Ad5 genetic background. Such mutant viruses included those that express E4orf4 proteins containing various individual point mutations, those defective entirely in E4orf4 expression, and a mutant expressing wild-type E4orf4 fused to the green fluorescent protein. E4orf4 protein was found to localize primarily in nuclear structures shown to be viral replication centers, in nucleoli, and in perinuclear bodies. Importantly, E4orf4 was shown not to be essential for virus growth in either human tumor or primary cells, at least in tissue culture. Unlike E4orf4-null virus, mutant <jats:italic>dl</jats:italic> 359 appeared to exhibit a gain-of-function phenotype that impairs virus growth. The <jats:italic>dl</jats:italic> 359 E4orf4 protein, which contains a large in-frame internal deletion, clustered in aggregates enriched in Hsp70 and proteasome components. In addition, the late viral mRNAs produced by <jats:italic>dl</jats:italic> 359 accumulated abnormally in a nuclear punctate pattern. Altogether, our results indicate that E4orf4 protein is not essential for virus growth in culture and that expression of the <jats:italic>dl</jats:italic> 359 E4orf4 product interferes with viral replication, presumably through interactions with structures in the nucleus. </jats:p> Localization and Importance of the Adenovirus E4orf4 Protein during Lytic Infection Journal of Virology |
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| title |
Localization and Importance of the Adenovirus E4orf4 Protein during Lytic Infection |
| title_unstemmed |
Localization and Importance of the Adenovirus E4orf4 Protein during Lytic Infection |
| title_full |
Localization and Importance of the Adenovirus E4orf4 Protein during Lytic Infection |
| title_fullStr |
Localization and Importance of the Adenovirus E4orf4 Protein during Lytic Infection |
| title_full_unstemmed |
Localization and Importance of the Adenovirus E4orf4 Protein during Lytic Infection |
| title_short |
Localization and Importance of the Adenovirus E4orf4 Protein during Lytic Infection |
| title_sort |
localization and importance of the adenovirus e4orf4 protein during lytic infection |
| topic |
Virology Insect Science Immunology Microbiology |
| url |
http://dx.doi.org/10.1128/jvi.01703-08 |
| publishDate |
2009 |
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1689-1699 |
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<jats:title>ABSTRACT</jats:title>
<jats:p>
The human adenovirus type 5 (Ad5) E4orf4 product has been studied extensively although in most cases as expressed from vectors in the absence of other viral products. Thus, relatively little is known about its role in the context of an adenovirus infection. Although considerable earlier work had indicated that the E4orf4 protein is not essential for replication, a recent study using
<jats:italic>dl</jats:italic>
359, an Ad5 mutant believed to produce a nonfunctional E4orf4 protein, suggested that E4orf4 is essential for virus growth in primary small-airway epithelial cells (C. O'Shea, et al., EMBO J. 24:1211-1221, 2005). Hence, to examine further the role of E4orf4 during virus infection, we generated for the first time a set of E4orf4 virus mutants in a common Ad5 genetic background. Such mutant viruses included those that express E4orf4 proteins containing various individual point mutations, those defective entirely in E4orf4 expression, and a mutant expressing wild-type E4orf4 fused to the green fluorescent protein. E4orf4 protein was found to localize primarily in nuclear structures shown to be viral replication centers, in nucleoli, and in perinuclear bodies. Importantly, E4orf4 was shown not to be essential for virus growth in either human tumor or primary cells, at least in tissue culture. Unlike E4orf4-null virus, mutant
<jats:italic>dl</jats:italic>
359 appeared to exhibit a gain-of-function phenotype that impairs virus growth. The
<jats:italic>dl</jats:italic>
359 E4orf4 protein, which contains a large in-frame internal deletion, clustered in aggregates enriched in Hsp70 and proteasome components. In addition, the late viral mRNAs produced by
<jats:italic>dl</jats:italic>
359 accumulated abnormally in a nuclear punctate pattern. Altogether, our results indicate that E4orf4 protein is not essential for virus growth in culture and that expression of the
<jats:italic>dl</jats:italic>
359 E4orf4 product interferes with viral replication, presumably through interactions with structures in the nucleus.
</jats:p> |
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| author | Miron, Marie-Joëlle, Blanchette, Paola, Groitl, Peter, Dallaire, Frederic, Teodoro, Jose G., Li, Suiyang, Dobner, Thomas, Branton, Philip E. |
| author_facet | Miron, Marie-Joëlle, Blanchette, Paola, Groitl, Peter, Dallaire, Frederic, Teodoro, Jose G., Li, Suiyang, Dobner, Thomas, Branton, Philip E., Miron, Marie-Joëlle, Blanchette, Paola, Groitl, Peter, Dallaire, Frederic, Teodoro, Jose G., Li, Suiyang, Dobner, Thomas, Branton, Philip E. |
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| description | <jats:title>ABSTRACT</jats:title> <jats:p> The human adenovirus type 5 (Ad5) E4orf4 product has been studied extensively although in most cases as expressed from vectors in the absence of other viral products. Thus, relatively little is known about its role in the context of an adenovirus infection. Although considerable earlier work had indicated that the E4orf4 protein is not essential for replication, a recent study using <jats:italic>dl</jats:italic> 359, an Ad5 mutant believed to produce a nonfunctional E4orf4 protein, suggested that E4orf4 is essential for virus growth in primary small-airway epithelial cells (C. O'Shea, et al., EMBO J. 24:1211-1221, 2005). Hence, to examine further the role of E4orf4 during virus infection, we generated for the first time a set of E4orf4 virus mutants in a common Ad5 genetic background. Such mutant viruses included those that express E4orf4 proteins containing various individual point mutations, those defective entirely in E4orf4 expression, and a mutant expressing wild-type E4orf4 fused to the green fluorescent protein. E4orf4 protein was found to localize primarily in nuclear structures shown to be viral replication centers, in nucleoli, and in perinuclear bodies. Importantly, E4orf4 was shown not to be essential for virus growth in either human tumor or primary cells, at least in tissue culture. Unlike E4orf4-null virus, mutant <jats:italic>dl</jats:italic> 359 appeared to exhibit a gain-of-function phenotype that impairs virus growth. The <jats:italic>dl</jats:italic> 359 E4orf4 protein, which contains a large in-frame internal deletion, clustered in aggregates enriched in Hsp70 and proteasome components. In addition, the late viral mRNAs produced by <jats:italic>dl</jats:italic> 359 accumulated abnormally in a nuclear punctate pattern. Altogether, our results indicate that E4orf4 protein is not essential for virus growth in culture and that expression of the <jats:italic>dl</jats:italic> 359 E4orf4 product interferes with viral replication, presumably through interactions with structures in the nucleus. </jats:p> |
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| spelling | Miron, Marie-Joëlle Blanchette, Paola Groitl, Peter Dallaire, Frederic Teodoro, Jose G. Li, Suiyang Dobner, Thomas Branton, Philip E. 0022-538X 1098-5514 American Society for Microbiology Virology Insect Science Immunology Microbiology http://dx.doi.org/10.1128/jvi.01703-08 <jats:title>ABSTRACT</jats:title> <jats:p> The human adenovirus type 5 (Ad5) E4orf4 product has been studied extensively although in most cases as expressed from vectors in the absence of other viral products. Thus, relatively little is known about its role in the context of an adenovirus infection. Although considerable earlier work had indicated that the E4orf4 protein is not essential for replication, a recent study using <jats:italic>dl</jats:italic> 359, an Ad5 mutant believed to produce a nonfunctional E4orf4 protein, suggested that E4orf4 is essential for virus growth in primary small-airway epithelial cells (C. O'Shea, et al., EMBO J. 24:1211-1221, 2005). Hence, to examine further the role of E4orf4 during virus infection, we generated for the first time a set of E4orf4 virus mutants in a common Ad5 genetic background. Such mutant viruses included those that express E4orf4 proteins containing various individual point mutations, those defective entirely in E4orf4 expression, and a mutant expressing wild-type E4orf4 fused to the green fluorescent protein. E4orf4 protein was found to localize primarily in nuclear structures shown to be viral replication centers, in nucleoli, and in perinuclear bodies. Importantly, E4orf4 was shown not to be essential for virus growth in either human tumor or primary cells, at least in tissue culture. Unlike E4orf4-null virus, mutant <jats:italic>dl</jats:italic> 359 appeared to exhibit a gain-of-function phenotype that impairs virus growth. The <jats:italic>dl</jats:italic> 359 E4orf4 protein, which contains a large in-frame internal deletion, clustered in aggregates enriched in Hsp70 and proteasome components. In addition, the late viral mRNAs produced by <jats:italic>dl</jats:italic> 359 accumulated abnormally in a nuclear punctate pattern. Altogether, our results indicate that E4orf4 protein is not essential for virus growth in culture and that expression of the <jats:italic>dl</jats:italic> 359 E4orf4 product interferes with viral replication, presumably through interactions with structures in the nucleus. </jats:p> Localization and Importance of the Adenovirus E4orf4 Protein during Lytic Infection Journal of Virology |
| spellingShingle | Miron, Marie-Joëlle, Blanchette, Paola, Groitl, Peter, Dallaire, Frederic, Teodoro, Jose G., Li, Suiyang, Dobner, Thomas, Branton, Philip E., Journal of Virology, Localization and Importance of the Adenovirus E4orf4 Protein during Lytic Infection, Virology, Insect Science, Immunology, Microbiology |
| title | Localization and Importance of the Adenovirus E4orf4 Protein during Lytic Infection |
| title_full | Localization and Importance of the Adenovirus E4orf4 Protein during Lytic Infection |
| title_fullStr | Localization and Importance of the Adenovirus E4orf4 Protein during Lytic Infection |
| title_full_unstemmed | Localization and Importance of the Adenovirus E4orf4 Protein during Lytic Infection |
| title_short | Localization and Importance of the Adenovirus E4orf4 Protein during Lytic Infection |
| title_sort | localization and importance of the adenovirus e4orf4 protein during lytic infection |
| title_unstemmed | Localization and Importance of the Adenovirus E4orf4 Protein during Lytic Infection |
| topic | Virology, Insect Science, Immunology, Microbiology |
| url | http://dx.doi.org/10.1128/jvi.01703-08 |