Article: Class II ADP-ribosylation factors are required for efficient secretion of dengue viruses
| Title | Class II ADP-ribosylation factors are required for efficient secretion of dengue viruses | ||||||
|---|---|---|---|---|---|---|---|
| Authors | Kudelko, M1 Brault, JB2 Kwok, K1 Li, MY1 Pardigon, N2 Peiris, JSM1 Bruzzone, R1 2 Despre, P2 Nal, B1 3 Wang, PG1 | ||||||
| Issue Date | 2012 | ||||||
| Publisher | American 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?] DOI: http://dx.doi.org/10.1074/jbc.M111.270579 | ||||||
| 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. | ||||||
| ISSN | 0021-9258 2011 Impact Factor: 4.773 2011 SCImago Journal Rankings: 0.793 | ||||||
| DOI | http://dx.doi.org/10.1074/jbc.M111.270579 | ||||||
| ISI Accession Number ID | WOS:000298682400074
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 | References in Scopus |
| dc.contributor.author | Kudelko, M | ||||||
|---|---|---|---|---|---|---|---|
| dc.contributor.author | Brault, JB | ||||||
| dc.contributor.author | Kwok, K | ||||||
| dc.contributor.author | Li, MY | ||||||
| dc.contributor.author | Pardigon, N | ||||||
| dc.contributor.author | Peiris, JSM | ||||||
| dc.contributor.author | Bruzzone, R | ||||||
| dc.contributor.author | Despre, P | ||||||
| dc.contributor.author | Nal, B | ||||||
| dc.contributor.author | Wang, PG | ||||||
| dc.date.accessioned | 2012-07-16T09:44:13Z | ||||||
| dc.date.available | 2012-07-16T09:44:13Z | ||||||
| dc.date.issued | 2012 | ||||||
| dc.description.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. | ||||||
| dc.description.nature | link_to_OA_fulltext | ||||||
| dc.identifier.citation | Journal Of Biological Chemistry, 2012, v. 287 n. 1, p. 767-777 [How to Cite?] DOI: http://dx.doi.org/10.1074/jbc.M111.270579 | ||||||
| dc.identifier.doi | http://dx.doi.org/10.1074/jbc.M111.270579 | ||||||
| dc.identifier.epage | 777 | ||||||
| dc.identifier.hkuros | 201706 | ||||||
| dc.identifier.isi | WOS:000298682400074
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. | ||||||
| dc.identifier.issn | 0021-9258 2011 Impact Factor: 4.773 2011 SCImago Journal Rankings: 0.793 | ||||||
| dc.identifier.issue | 1 | ||||||
| dc.identifier.pmid | 22105072 | ||||||
| dc.identifier.scopus | eid_2-s2.0-84855290006 | ||||||
| dc.identifier.spage | 767 | ||||||
| dc.identifier.uri | http://hdl.handle.net/10722/152622 | ||||||
| dc.identifier.volume | 287 | ||||||
| dc.language | eng | ||||||
| dc.publisher | American Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/ | ||||||
| dc.publisher.place | United States | ||||||
| dc.relation.ispartof | Journal of Biological Chemistry | ||||||
| dc.relation.references | References in Scopus | ||||||
| dc.title | Class II ADP-ribosylation factors are required for efficient secretion of dengue viruses | ||||||
| dc.type | Article |
Author Affiliations
- The University of Hong Kong
- Institut Pasteur, Paris
- Brunel University