Subcellular localization and membrane topology of the Dengue virus type 2 Non-structural protein 4B - PubMed (original) (raw)
Comparative Study
. 2006 Mar 31;281(13):8854-63.
doi: 10.1074/jbc.M512697200. Epub 2006 Jan 25.
Affiliations
- PMID: 16436383
- DOI: 10.1074/jbc.M512697200
Free article
Comparative Study
Subcellular localization and membrane topology of the Dengue virus type 2 Non-structural protein 4B
Sven Miller et al. J Biol Chem. 2006.
Free article
Abstract
Dengue virus (DV) is a member of the family Flaviviridae. These positive strand RNA viruses encode a polyprotein that is processed in case of DV into 10 proteins. Although for most of these proteins distinct functions have been defined, this is less clear for the highly hydrophobic non-structural protein (NS) 4B. Despite its possible role as an antagonist of the interferon-induced antiviral response, this protein may play an additional more direct role for viral replication. In this study we determined the subcellular localization, membrane association, and membrane topology of DV NS4B. We found that NS4B resides primarily in cytoplasmic foci originating from the endoplasmic reticulum. NS4B colocalizes with NS3 and double-stranded RNA, an intermediate of viral replication, arguing that NS4B is part of the membrane-bound viral replication complex. Biochemical analysis revealed that NS4B is an integral membrane protein, and that its preceding 2K signal sequence is not required for this integration. We identified three membrane-spanning segments in the COOH-terminal part of NS4B that are sufficient to target a cytosolic marker protein to intracellular membranes. Furthermore, we established a membrane topology model of NS4B in which the NH2-terminal part of the protein is localized in the endoplasmic reticulum lumen, whereas the COOH-terminal part is composed of three trans-membrane domains with the COOH-terminal tail localized in the cytoplasm. This topology model provides a good starting point for a detailed investigation of the function of NS4B in the DV life cycle.
Similar articles
- The non-structural protein 4A of dengue virus is an integral membrane protein inducing membrane alterations in a 2K-regulated manner.
Miller S, Kastner S, Krijnse-Locker J, Bühler S, Bartenschlager R. Miller S, et al. J Biol Chem. 2007 Mar 23;282(12):8873-82. doi: 10.1074/jbc.M609919200. Epub 2007 Feb 2. J Biol Chem. 2007. PMID: 17276984 - A novel interaction between dengue virus nonstructural protein 1 and the NS4A-2K-4B precursor is required for viral RNA replication but not for formation of the membranous replication organelle.
Płaszczyca A, Scaturro P, Neufeldt CJ, Cortese M, Cerikan B, Ferla S, Brancale A, Pichlmair A, Bartenschlager R. Płaszczyca A, et al. PLoS Pathog. 2019 May 9;15(5):e1007736. doi: 10.1371/journal.ppat.1007736. eCollection 2019 May. PLoS Pathog. 2019. PMID: 31071189 Free PMC article. - Topology of the membrane-associated hepatitis C virus protein NS4B.
Lundin M, Monné M, Widell A, Von Heijne G, Persson MA. Lundin M, et al. J Virol. 2003 May;77(9):5428-38. doi: 10.1128/jvi.77.9.5428-5438.2003. J Virol. 2003. PMID: 12692244 Free PMC article. - The Dengue Virus Replication Complex: From RNA Replication to Protein-Protein Interactions to Evasion of Innate Immunity.
Lescar J, Soh S, Lee LT, Vasudevan SG, Kang C, Lim SP. Lescar J, et al. Adv Exp Med Biol. 2018;1062:115-129. doi: 10.1007/978-981-10-8727-1_9. Adv Exp Med Biol. 2018. PMID: 29845529 Review. - Dengue virus NS4B protein as a target for developing antivirals.
Li Q, Kang C. Li Q, et al. Front Cell Infect Microbiol. 2022 Aug 9;12:959727. doi: 10.3389/fcimb.2022.959727. eCollection 2022. Front Cell Infect Microbiol. 2022. PMID: 36017362 Free PMC article. Review.
Cited by
- Development of antibody-based assays for high throughput discovery and mechanistic study of antiviral agents against yellow fever virus.
Gao Z, Zhang L, Ma J, Jurado A, Hong SH, Guo JT, Rice CM, MacDonald MR, Chang J. Gao Z, et al. Antiviral Res. 2020 Oct;182:104907. doi: 10.1016/j.antiviral.2020.104907. Epub 2020 Aug 14. Antiviral Res. 2020. PMID: 32798604 Free PMC article. - Interaction of TIA-1/TIAR with West Nile and dengue virus products in infected cells interferes with stress granule formation and processing body assembly.
Emara MM, Brinton MA. Emara MM, et al. Proc Natl Acad Sci U S A. 2007 May 22;104(21):9041-6. doi: 10.1073/pnas.0703348104. Epub 2007 May 14. Proc Natl Acad Sci U S A. 2007. PMID: 17502609 Free PMC article. - Role of annexin A2 in the production of infectious hepatitis C virus particles.
Backes P, Quinkert D, Reiss S, Binder M, Zayas M, Rescher U, Gerke V, Bartenschlager R, Lohmann V. Backes P, et al. J Virol. 2010 Jun;84(11):5775-89. doi: 10.1128/JVI.02343-09. Epub 2010 Mar 24. J Virol. 2010. PMID: 20335258 Free PMC article. - Structures and Dynamics of Dengue Virus Nonstructural Membrane Proteins.
Li Q, Kang C. Li Q, et al. Membranes (Basel). 2022 Feb 17;12(2):231. doi: 10.3390/membranes12020231. Membranes (Basel). 2022. PMID: 35207152 Free PMC article. Review. - Roles of Non-Structural Protein 4A in Flavivirus Infection.
Klaitong P, Smith DR. Klaitong P, et al. Viruses. 2021 Oct 15;13(10):2077. doi: 10.3390/v13102077. Viruses. 2021. PMID: 34696510 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Miscellaneous