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Article: Class II ADP-ribosylation factors are required for efficient secretion of dengue viruses

TitleClass II ADP-ribosylation factors are required for efficient secretion of dengue viruses
Authors
Issue Date2012
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
Citation
Journal Of Biological Chemistry, 2012, v. 287 n. 1, p. 767-777 How to Cite?
Abstract
Identification and characterization of virus-host interactions are very important steps toward a better understanding of the molecular mechanisms responsible for disease progression and pathogenesis. To date, very few cellular factors involved in the life cycle of flaviviruses, which are important human pathogens, have been described. In this study, we demonstrate a crucial role for class II Arf proteins (Arf4 and Arf5) in the dengue flavivirus life cycle. We show that simultaneous depletion of Arf4 and Arf5 blocks recombinant subviral particle secretion for all four dengue serotypes. Immunostaining analysis suggests that class II Arf proteins are required at an early pre-Golgi step for dengue virus secretion. Using a horseradish peroxidase protein fused to a signal peptide, we show that class II Arfs act specifically on dengue virus secretion without altering the secretion of proteins through the constitutive secretory pathway. Co-immunoprecipitation data demonstrate that the dengue prM glycoprotein interacts with class II Arf proteins but not through its C-terminal VXPX motif. Finally, experiments performed with replication-competent dengue and yellow fever viruses demonstrate that the depletion of class II Arfs inhibits virus secretion, thus confirming their implication in the virus life cycle, although data obtained with West Nile virus pointed out the differences in virus-host interactions among flaviviruses. Our findings shed new light on a molecular mechanism used by dengue viruses during the late stages of the life cycle and demonstrate a novel function for class II Arf proteins. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/152622
ISSN
2013 Impact Factor: 4.600
ISI Accession Number ID
Funding AgencyGrant Number
Research Fund for Control of Infectious Diseases of Hong KongRFCID 08070952
RFCID 10091312
BNP Paribas Corporate and Investment Banking
Funding Information:

This work was supported by Research Fund for Control of Infectious Diseases of Hong Kong Grants RFCID 08070952 and RFCID 10091312 and by a donation from BNP Paribas Corporate and Investment Banking.

References

 

Author Affiliations
  1. The University of Hong Kong
  2. Institut Pasteur, Paris
  3. Brunel University
DC FieldValueLanguage
dc.contributor.authorKudelko, Men_HK
dc.contributor.authorBrault, JBen_HK
dc.contributor.authorKwok, Ken_HK
dc.contributor.authorLi, MYen_HK
dc.contributor.authorPardigon, Nen_HK
dc.contributor.authorPeiris, JSMen_HK
dc.contributor.authorBruzzone, Ren_HK
dc.contributor.authorDespre, Pen_HK
dc.contributor.authorNal, Ben_HK
dc.contributor.authorWang, PGen_HK
dc.date.accessioned2012-07-16T09:44:13Z-
dc.date.available2012-07-16T09:44:13Z-
dc.date.issued2012en_HK
dc.identifier.citationJournal Of Biological Chemistry, 2012, v. 287 n. 1, p. 767-777en_HK
dc.identifier.issn0021-9258en_HK
dc.identifier.urihttp://hdl.handle.net/10722/152622-
dc.description.abstractIdentification and characterization of virus-host interactions are very important steps toward a better understanding of the molecular mechanisms responsible for disease progression and pathogenesis. To date, very few cellular factors involved in the life cycle of flaviviruses, which are important human pathogens, have been described. In this study, we demonstrate a crucial role for class II Arf proteins (Arf4 and Arf5) in the dengue flavivirus life cycle. We show that simultaneous depletion of Arf4 and Arf5 blocks recombinant subviral particle secretion for all four dengue serotypes. Immunostaining analysis suggests that class II Arf proteins are required at an early pre-Golgi step for dengue virus secretion. Using a horseradish peroxidase protein fused to a signal peptide, we show that class II Arfs act specifically on dengue virus secretion without altering the secretion of proteins through the constitutive secretory pathway. Co-immunoprecipitation data demonstrate that the dengue prM glycoprotein interacts with class II Arf proteins but not through its C-terminal VXPX motif. Finally, experiments performed with replication-competent dengue and yellow fever viruses demonstrate that the depletion of class II Arfs inhibits virus secretion, thus confirming their implication in the virus life cycle, although data obtained with West Nile virus pointed out the differences in virus-host interactions among flaviviruses. Our findings shed new light on a molecular mechanism used by dengue viruses during the late stages of the life cycle and demonstrate a novel function for class II Arf proteins. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.en_HK
dc.languageengen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/en_HK
dc.relation.ispartofJournal of Biological Chemistryen_HK
dc.titleClass II ADP-ribosylation factors are required for efficient secretion of dengue virusesen_HK
dc.typeArticleen_HK
dc.identifier.emailPeiris, JSM: malik@hkucc.hku.hken_HK
dc.identifier.emailBruzzone, R: bruzzone@hkucc.hku.hken_HK
dc.identifier.emailNal, B: bnal@hkucc.hku.hken_HK
dc.identifier.authorityPeiris, JSM=rp00410en_HK
dc.identifier.authorityBruzzone, R=rp01442en_HK
dc.identifier.authorityNal, B=rp00541en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1074/jbc.M111.270579en_HK
dc.identifier.pmid22105072en_HK
dc.identifier.scopuseid_2-s2.0-84855290006en_HK
dc.identifier.hkuros201706en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84855290006&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume287en_HK
dc.identifier.issue1en_HK
dc.identifier.spage767en_HK
dc.identifier.epage777en_HK
dc.identifier.isiWOS:000298682400074-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridKudelko, M=35083703200en_HK
dc.identifier.scopusauthoridBrault, JB=53981059700en_HK
dc.identifier.scopusauthoridKwok, K=19337480200en_HK
dc.identifier.scopusauthoridLi, MY=54881442700en_HK
dc.identifier.scopusauthoridPardigon, N=6603068333en_HK
dc.identifier.scopusauthoridPeiris, JSM=7005486823en_HK
dc.identifier.scopusauthoridBruzzone, R=7006793327en_HK
dc.identifier.scopusauthoridDespre, P=54881251300en_HK
dc.identifier.scopusauthoridNal, B=6506672380en_HK
dc.identifier.scopusauthoridWang, PG=7405460758en_HK

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