Nuclear localization of dengue virus capsid protein is required for DAXX interaction and apoptosis

Netsawang, Janjuree; Noisakran, Sansanee; Puttikhunt, Chunya; Kasinrerk, Watchara; Wongwiwat, Wiyada; Malasit, Prida; Yenchitsomanus, Pa‐thai; Limjindaporn, Thawornchai

doi:10.1016/j.virusres.2009.11.012

Cited by 80 publications

(70 citation statements)

References 41 publications

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“…It has been reported previously that the C protein of flaviviruses is involved in the induction of apoptosis and the breakdown of cellular tight junctions (26,37,44). A growing number of host proteins that interact with flavivirus C proteins have been reported (4,5,18,28). For instance, by use of twohybrid systems, several cellular proteins that interact with WNV C have been identified (29,42).…”

Section: Discussionmentioning

confidence: 99%

Uncoupling cis -Acting RNA Elements from Coding Sequences Revealed a Requirement of the N-Terminal Region of Dengue Virus Capsid Protein in Virus Particle Formation

Samsa

Mondotte

Caramelo

et al. 2012

J Virol

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Little is known about the mechanism of flavivirus genome encapsidation. Here, functional elements of the dengue virus (DENV) capsid (C) protein were investigated. Study of the N-terminal region of DENV C has been limited by the presence of overlapping cis-acting RNA elements within the protein-coding region. To dissociate these two functions, we used a recombinant DENV RNA with a duplication of essential RNA structures outside the C coding sequence. By the use of this system, the highly conserved amino acids FNML, which are encoded in the RNA cyclization sequence 5=CS, were found to be dispensable for C function. In contrast, deletion of the N-terminal 18 amino acids of C impaired DENV particle formation. Two clusters of basic residues (R5-K6-K7-R9 and K17-R18-R20-R22) were identified as important. A systematic mutational analysis indicated that a high density of positive charges, rather than particular residues at specific positions, was necessary. Furthermore, a differential requirement of N-terminal sequences of C for viral particle assembly was observed in mosquito and human cells. While no viral particles were observed in human cells with a virus lacking the first 18 residues of C, DENV propagation was detected in mosquito cells, although to a level about 50-fold less than that observed for a wild-type (WT) virus. We conclude that basic residues at the N terminus of C are necessary for efficient particle formation in mosquito cells but that they are crucial for propagation in human cells. This is the first report demonstrating that the N terminus of C plays a role in DENV particle formation. In addition, our results suggest that this function of C is differentially modulated in different host cells. D engue virus (DENV) is a member of the genus Flavivirus in the familyFlaviviridae, together with other important pathogens such as yellow fever virus (YFV), West Nile virus (WNV), Saint Louis encephalitis virus (SLEV), and Japanese encephalitis virus (JEV). DENV is the most significant mosquito-borne human viral pathogen worldwide, infecting more than 50 million people each year (41). Despite the urgent medical need to control DENV infections, vaccines and antivirals are still unavailable.DENV has a plus-stranded RNA genome of about 11 kb. The single open reading frame encodes a polyprotein that is co-and posttranslationally processed by host and viral proteases. This processing yields three structural proteins (C, prM, and E) and at least seven nonstructural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) (22). The coding sequence is flanked by highly structured 5= and 3= untranslated regions (UTRs) (11). In recent years, a number of cis-acting RNA elements that modulate viral RNA amplification have been identified in the viral genome (for a review, see reference 38). Viral RNA synthesis is catalyzed by the RNA-dependent RNA-polymerase activity of the viral protein NS5 and requires interaction with a 5=-end promoter element (9, 10, 13). During flavivirus morphogenesis, the newly synthesized viral RNA is r...

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Section: Discussionmentioning

confidence: 99%

Uncoupling cis -Acting RNA Elements from Coding Sequences Revealed a Requirement of the N-Terminal Region of Dengue Virus Capsid Protein in Virus Particle Formation

Samsa

Mondotte

Caramelo

et al. 2012

J Virol

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“…The presence of DENV C in the nucleoli of infected cells has also been observed in several prior studies (22-24, 27, 84). In addition, the DENV C protein has been shown to interact with a number of other nuclear proteins, including DAXX, hnRNP-K, and Core histones (27)(28)(29). There is evidence suggesting a role for nuclear DENV C in induction of FAS-mediated apoptosis in hepatoma cells (27).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the DENV C protein has been shown to interact with a number of other nuclear proteins, including DAXX, hnRNP-K, and Core histones (27)(28)(29). There is evidence suggesting a role for nuclear DENV C in induction of FAS-mediated apoptosis in hepatoma cells (27). However, it has also been reported that DENV C may act to inhibit apoptosis through interactions with cyclophilin-binding ligand (30).…”

Section: Discussionmentioning

confidence: 99%

“…The role of the C protein in the nucleus has not yet been elucidated. However, it has been shown to interact with a number of (predominantly nuclear) host proteins, including hnRNP-K, DAXX, and Core histones (26)(27)(28)(29)(30). The cellular protein nucleolin (NCL) is found primarily within the nucleolus but can also be found in the cytoplasm and on the plasma membrane (31)(32)(33).…”

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confidence: 99%

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Nucleolin Interacts with the Dengue Virus Capsid Protein and Plays a Role in Formation of Infectious Virus Particles

Balinsky

Schmeisser

Ganesan

et al. 2013

J Virol

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Dengue virus (DENV), a member of the genus Flavivirus, causes a spectrum of disease in humans that can range from a mild febrile illness to potentially fatal hemorrhage or shock syndromes. Four serotypes of DENV (DENV-1, -2, -3, and -4) are transmitted by the bite of a mosquito vector and are responsible for more than 50 million infections each year. Infection with one DENV serotype does not confer lasting immunity to the others (1-3). The most severe clinical manifestations of dengue are associated with secondary infections by a heterologous DENV serotype (2). Increasing urbanization, cocirculation of multiple DENV serotypes within the same geographic area, and expansion of its insect vector contribute to the increasing importance of dengue to global health (2, 3).DENV contains a positive-sense single-stranded RNA (ssRNA) genome that is translated as a single open reading frame. The resulting polyprotein is cleaved by virus and host proteases into three structural and at least seven nonstructural proteins (4, 5). The capsid (C) protein functions as a structural component of the DENV virion, encapsulating the ssRNA genome of the virus (4, 5). The DENV C protein is composed of four alpha helices with an unstructured amino terminus and forms antiparallel homodimers.

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“…33 As a novel histone chaperone and a product of an interferon-c-induced gene, Daxx has been extensively implicated in virus infection and T-cell activation. [34][35][36][37][38][39][40][41][42][43] Recent studies demonstrated that MST1 and Daxx interact with each other to mediate interferon-c-induced apoptosis in microglia, which plays a critical role during inflammation. 44 In this process, Daxx directly binds to MST1 and regulates its homooligomerization, activation and nuclear translocation.…”

Section: Gck-ii Kinases Regulate Lymphocyte Adhesion Migration Prolmentioning

confidence: 99%

Germinal center kinases in immune regulation

Yin

Shi

et al. 2012

Cell Mol Immunol

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Nuclear localization of dengue virus capsid protein is required for DAXX interaction and apoptosis

Cited by 80 publications

References 41 publications

Uncoupling cis -Acting RNA Elements from Coding Sequences Revealed a Requirement of the N-Terminal Region of Dengue Virus Capsid Protein in Virus Particle Formation

Uncoupling cis -Acting RNA Elements from Coding Sequences Revealed a Requirement of the N-Terminal Region of Dengue Virus Capsid Protein in Virus Particle Formation

Nucleolin Interacts with the Dengue Virus Capsid Protein and Plays a Role in Formation of Infectious Virus Particles

Germinal center kinases in immune regulation

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