Sensitization to Fas-mediated apoptosis by dengue virus capsid protein

Limjindaporn, Thawornchai; Netsawang, Janjuree; Noisakran, Sansanee; Thiemmeca, Somchai; Wongwiwat, Wiyada; Sudsaward, Sangkab; Avirutnan, Panisadee; Puttikhunt, Chunya; Kasinrerk, Watchara; Sriburi, Rungtawan; Sittisombut, Nopporn; Yenchitsomanus, Pa‐thai; Malasit, Prida

doi:10.1016/j.bbrc.2007.07.194

Cited by 53 publications

(45 citation statements)

References 33 publications

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“…The DEN core protein has been shown to interact with hnRNP K and to regulate C/EBP-␤-mediated transcription to modify the host cell environment by regulating the expression of pro-and antiviral factors for viral propagation (7). In addition, the core proteins of DEN, WNV, and hepatitis C virus (HCV), which belongs to the genus Hepacivirus within the family Flaviviridae, have functions of inducing or inhibiting the apoptosis associated with host factors, suggesting that the core protein of flaviviruses participates not only in viral assembly (as a structural protein) but also in pathogenesis (as a nonstructural protein) (13,34,43,58,70). The flavivirus core protein is not essential for RNA replication, since NS proteins alone are sufficient for efficient replication of the subgenomic viral RNA (24), while the core protein has been suggested to augment viral RNA replication (48).…”

Section: Discussionmentioning

confidence: 99%

Heterogeneous Nuclear Ribonucleoprotein A2 Participates in the Replication of Japanese Encephalitis Virus through an Interaction with Viral Proteins and RNA

Katoh

Mori

Kambara

et al. 2011

J Virol

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Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that is kept in a zoonotic transmission cycle between pigs and mosquitoes. JEV causes infection of the central nervous system with a high mortality rate in dead-end hosts, including humans. Many studies have suggested that the flavivirus core protein is not only a component of nucleocapsids but also an important pathogenic determinant. In this study, we identified heterogeneous nuclear ribonucleoprotein A2 (hnRNP A2) as a binding partner of the JEV core protein by pulldown purification and mass spectrometry. Reciprocal coimmunoprecipitation analyses in transfected and infected cells confirmed a specific interaction between the JEV core protein and hnRNP A2. Expression of the JEV core protein induced cytoplasmic retention of hnRNP A2 in JEV subgenomic replicon cells. Small interfering RNA (siRNA)-mediated knockdown of hnRNP A2 resulted in a 90% reduction of viral RNA replication in cells infected with JEV, and the reduction was cancelled by the expression of an siRNA-resistant hnRNP A2 mutant. In addition to the core protein, hnRNP A2 also associated with JEV nonstructural protein 5, which has both methyltransferase and RNA-dependent RNA polymerase activities, and with the 5-untranslated region of the negative-sense JEV RNA. During one-step growth, synthesis of both positive-and negativestrand JEV RNAs was delayed by the knockdown of hnRNP A2. These results suggest that hnRNP A2 plays an important role in the replication of JEV RNA through the interaction with viral proteins and RNA.Japanese encephalitis virus (JEV) belongs to the genus Flavivirus within the family Flaviviridae. Members of the genus Flavivirus are predominantly arthropod-borne viruses, such as dengue virus (DEN), West Nile virus (WNV), yellow fever virus (YFV), and tick-borne encephalitis virus, and frequently cause significant morbidity and mortality in mammals and birds (46). JEV is distributed in the south and southeast regions of Asia and is kept in a zoonotic transmission cycle between pigs or birds and mosquitoes (46,69). JEV spreads to dead-end hosts, including humans, through the bite of JEVinfected mosquitoes and causes infection of the central nervous system, with a high mortality rate (46). JEV has a singlestranded positive-strand RNA genome of approximately 11 kb, which is capped at the 5Ј end but lacks modification of the 3Ј terminus by polyadenylation (38). The genomic RNA carries a single large open reading frame, and a polyprotein translated from the genome is cleaved co-and posttranslationally by host and viral proteases to yield three structural proteins-the core, precursor membrane, and envelope protein-and seven nonstructural (NS) proteins-NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5 (61).The core protein of flaviviruses has RNA-binding activity through basic amino acid clusters located in both the amino and carboxyl termini, indicating that the core protein forms a nucleocapsid interacting with viral RNA (23). In spite of the replication of flaviviruses in the cyto...

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Section: Discussionmentioning

confidence: 99%

Heterogeneous Nuclear Ribonucleoprotein A2 Participates in the Replication of Japanese Encephalitis Virus through an Interaction with Viral Proteins and RNA

Katoh

Mori

Kambara

et al. 2011

J Virol

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“…The lack of DENV-2 CA-induced cell death contrasts with WNV CA protein which can induce cell death via activation of the caspase-9-caspase-3 cascade (Yang et al, 2002(Yang et al, , 2008, and with the HCV core protein which has been reported to either inhibit TNF-astimulated NF-kB activation (Shrivastava et al, 1998) and induce cell death (Zhu et al, 1998(Zhu et al, , 2001, or to inhibit cell death by activation of the caspase inhibitors, inhibitor of caspase-activated DNase (Sacco et al, 2003) and FASassociated death domain (FADD)-like interleukin-1b converting enzyme (Saito et al, 2006). DENV-2 CA can interact with the Daxx protein in vitro and induce Fasmediated apoptosis of DENV-2-infected liver cells (Limjindaporn et al, 2007). Other DENV-2 proteins such as NS3, NS2B-NS3 protease (Shafee & AbuBakar, 2003) or membrane protein (Catteau et al, 2003) have been reported to induce apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Tumour necrosis factor alpha (TNF- ) stimulation of cells with established dengue virus type 2 infection induces cell death that is accompanied by a reduced ability of TNF- to activate nuclear factor B and reduced sphingosine kinase-1 activity

Wati

Rawlinson

Ivanov

et al. 2010

Journal of General Virology

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“…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).…”

mentioning

confidence: 99%

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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Sensitization to Fas-mediated apoptosis by dengue virus capsid protein

Cited by 53 publications

References 33 publications

Heterogeneous Nuclear Ribonucleoprotein A2 Participates in the Replication of Japanese Encephalitis Virus through an Interaction with Viral Proteins and RNA

Heterogeneous Nuclear Ribonucleoprotein A2 Participates in the Replication of Japanese Encephalitis Virus through an Interaction with Viral Proteins and RNA

Tumour necrosis factor alpha (TNF- ) stimulation of cells with established dengue virus type 2 infection induces cell death that is accompanied by a reduced ability of TNF- to activate nuclear factor B and reduced sphingosine kinase-1 activity

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

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