RNA Interference Mediated Inhibition of Dengue Virus Multiplication and Entry in HepG2 Cells

Alhoot, Mohammed Abdelfatah; Wang, Seok Mui; Sekaran, Shamala Devi

doi:10.1371/journal.pone.0034060

Cited by 45 publications

(38 citation statements)

References 86 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Regarding hepatic cells, small interfering RNAs (siRNA) silencing experiments revealed that all DENV serotypes enter Huh7 cells through clathrin-mediated endocytosis, and that DENV-2 requires early to late endosome trafficking (Ang et al, 2010). Clathrin-mediated-endocytosis dependence of DENV entry in HepG2 cells was demonstrated by siRNA silencing of target genes as well (Alhoot, Wang and Sekaran 2012). Macropinocytosis was also identified as one of the DENV entry pathways in these cells, although clathrin-mediated endocytosis was the predominant entry route (Suksanpaisan, Susantad and Smith 2009).…”

Section: Entry Pathwaysmentioning

confidence: 99%

Receptors and routes of dengue virus entry into the host cells

Cruz-Oliveira

Freire

Conceição

et al. 2015

FEMS Microbiology Reviews

259

211

View full text Add to dashboard Cite

One-sentence summary: This review addresses the structural rearrangements of dengue virus proteins and their functions during virus entry into the host cells, exploring (a) the cellular elements involved in virus binding to mammalian and mosquito cells, (b) the internalization routes that ultimately lead to virus entry into the cell and (c) the mechanisms by which viral genome gain access to the cytoplasm, including original insights from our recent work that supports the hypothesis that the capsid protein has a role in this process. Editor: Urs Greber ABSTRACTDengue is the most prevalent arthropod-borne viral disease, caused by dengue virus, a member of the Flaviviridae family. Its worldwide incidence is now a major health problem, with 2.5 billion people living in risk areas. In this review, we integrate the structural rearrangements of each viral protein and their functions in all the steps of virus entry into the host cells. We describe in detail the putative receptors and attachment factors in mammalian and mosquito cells, and the recognition of viral immunocomplexes via Fcγ receptor in immune cells. We also discuss that virus internalization might occur through distinct entry pathways, including clathrin-mediated or non-classical clathrin-independent endocytosis, depending on the host cell and virus serotype or strain. The implications of viral maturation in virus entry are also explored. Finally, we discuss the mechanisms of viral genome access to the cytoplasm. This includes the role of low pH-induced conformational changes in the envelope protein that mediate membrane fusion, and original insights raised by our recent work that supports the hypothesis that capsid protein would also be an active player in this process, acting on viral genome translocation into the cytoplasm.

show abstract

Section: Entry Pathwaysmentioning

confidence: 99%

Receptors and routes of dengue virus entry into the host cells

Cruz-Oliveira

Freire

Conceição

et al. 2015

FEMS Microbiology Reviews

259

211

View full text Add to dashboard Cite

show abstract

“…Among these lectins, dendritic cellspecific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) has been identified as a DENV receptor in immature dendritic HepG2 Laminin receptor 1 [40] GRP78 2 [37][38][39] K562 Glycosphingolipid 1-4 [44] HUVEC Heparan sulfate 4…”

Section: Receptors In Mammalian Cellsmentioning

confidence: 99%

Dengue Virus Entry and Trafficking: Perspectives as Antiviral Target for Prevention and Therapy

2015

View full text Add to dashboard Cite

Dengue virus (DENV) is the etiological agent of the most important human viral infection transmitted by mosquitoes in the world. In spite of the serious health threat that dengue represents, at present there are no vaccine or antiviral agents available and treatment of patients consists of supportive therapy. This review will focus on the process of DENV entry into the host cell as a potential target for antiviral therapy. The recent advances in the knowledge of viral and cellular molecules and mechanisms involved in binding, internalization and trafficking of DENV into the host cell until virion uncoating are discussed, together with an overview of the strategies and compounds evaluated for development of antiviral agents targeted to DENV entry. KeywordsDengue is currently the most widespread arbovirosis in the world, with a particularly high prevalence in diverse tropical and subtropical regions of America and Asia [1]. The WHO estimates an occurrence of 50-100 million annual infections, but more recent modelling evaluations increased the number of new possible infections to 390 million per year [2]. There are four serotypes of dengue viruses (DENV), designated DENV-1 to DENV-4, that cocirculate and are transmitted to humans by the bites of the mosquitoes Aedes aegypti and Aedes albopictus. Precisely, the failure in the programs for control of the mosquito vector is one of the reasons for the explosive re-emergence and global spread of dengue in the last few decades in >100 countries, resulting in a serious public health challenge.All serotypes can produce either an inapparent infection or a wide spectrum of clinical outcomes ranging from a mild febrile illness known as dengue fever (DF) to the more severe and life-threatening forms of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) [3]. The initial infection with one DENV serotype leads to lifelong protection against homologous reinfection, but only brief and partial protection against infection with other serotypes. In fact, the secondary infection with a heterologous serotype is considered a risk factor for developing DHF and DSS. These severe clinical manifestations have been associated to the phenomenon known as antibody-dependent enhancement (ADE) [3]. In this process, the antibodies elicited by the primary infection bind to the heterotypic virus without neutralization of viral infectivity, and these immune complexes are opsonized into Fc-receptor positive cells leading to an increase in DENV replication and pathogenesis [4,5].DENV is a member of the genus Flavivirus in the family Flaviviridae. The virion is a small spherical particle, 40-50 nm in diameter, containing a single-stranded positive sense RNA included in an inner nucleocapsid and surrounded by a lipid envelope. The virus genome codes for a single polyprotein that is cleaved into three structural proteins (the capsid protein C,

show abstract

“…It is possible that the entry pathway(s) utilized by the virus may be cell type dependent. Two recent RNA interference studies for dengue virus entry and multiplication into monocytes and HepG2 cells show dependence on clathrin heavy chain (CHC) and dyamin-2 (15,16).…”

mentioning

confidence: 99%

Japanese Encephalitis Virus Infects Neuronal Cells through a Clathrin-Independent Endocytic Mechanism

Kalia

Khasa

Sharma

et al. 2013

J Virol

122

104

View full text Add to dashboard Cite

Japanese encephalitis virus (JEV) is a mosquito-borne pathogenic flavivirus responsible for acute viral encephalitis in humans. The cellular entry of JEV is poorly characterized in terms of molecular requirements and pathways. Here we present a systematic study of the internalization mechanism of JEV in fibroblasts and neuroblastoma cells. To verify the roles of distinct pathways of cell entry, we used fluorescently labeled virus particles, a combination of pharmacological inhibitors, RNA interference (RNAi), and dominant-negative (DN) mutants of regulatory proteins involved in endocytosis. Our study demonstrates that JEV infects fibroblasts in a clathrin-dependent manner, but it deploys a clathrin-independent mechanism to infect neuronal cells. The clathrin-independent pathway requires dynamin and plasma membrane cholesterol. Virus binding to neuronal cells leads to rapid actin rearrangements and an intact and dynamic actin cytoskeleton, and the small GTPase RhoA plays an important role in viral entry. Immunofluorescence analysis of viral colocalization with endocytic markers showed that JEV traffics through Rab5-positive early endosomes and that release of the viral nucleocapsid occurs at the level of the early and not the late endosomes.

show abstract

RNA Interference Mediated Inhibition of Dengue Virus Multiplication and Entry in HepG2 Cells

Cited by 45 publications

References 86 publications

Receptors and routes of dengue virus entry into the host cells

Receptors and routes of dengue virus entry into the host cells

Dengue Virus Entry and Trafficking: Perspectives as Antiviral Target for Prevention and Therapy

Japanese Encephalitis Virus Infects Neuronal Cells through a Clathrin-Independent Endocytic Mechanism

Contact Info

Product

Resources

About