Comparative analysis of full genomic sequences among different genotypes of dengue virus type 3

King, Chwan-Chuen; Chao, Day‐Yu; Chien, Li‐Jung; Chang, Gwong‐Jen J.; Lin, Tao; Wu, Yin-Chang; Huang, Jiansheng

doi:10.1186/1743-422x-5-63

Cited by 46 publications

(48 citation statements)

References 43 publications

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“…Although there is significant genetic variation throughout the genomes of strains of the DENV-3 serotype, the diversity is greatest within the E protein (5,23,26,57), the target of the majority of neutralizing MAbs. The DENV-3 serotype is seg- c Four-to 5-week-old AG129 mice were passively administered 500 g of the indicated MAbs 1 day before infection with 5 ϫ 10 3 PFU of strain 16652 by an i.c.…”

Section: Discussionmentioning

confidence: 99%

Genotype-Specific Neutralization and Protection by Antibodies against Dengue Virus Type 3

Brien

Austin

Sukupolvi-Petty

et al. 2010

J Virol

133

148

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Dengue viruses (DENV) comprise a family of related positive-strand RNA viruses that infect up to 100 million people annually. Currently, there is no approved vaccine or therapy to prevent infection or diminish disease severity. Protection against DENV is associated with the development of neutralizing antibodies that recognize the viral envelope (E) protein. Here, with the goal of identifying monoclonal antibodies (MAbs) that can function as postexposure therapy, we generated a panel of 82 new MAbs against DENV-3, including 24 highly neutralizing MAbs. Using yeast surface display, we localized the epitopes of the most strongly neutralizing MAbs to the lateral ridge of domain III (DIII) of the DENV type 3 (DENV-3) E protein. While several MAbs functioned prophylactically to prevent DENV-3-induced lethality in a stringent intracranial-challenge model of mice, only three MAbs exhibited therapeutic activity against a homologous strain when administered 2 days after infection. Remarkably, no MAb in our panel protected prophylactically against challenge by a strain from a heterologous DENV-3 genotype. Consistent with this, no single MAb neutralized efficiently the nine different DENV-3 strains used in this study, likely because of the sequence variation in DIII within and between genotypes. Our studies suggest that strain diversity may limit the efficacy of MAb therapy or tetravalent vaccines against DENV, as neutralization potency generally correlated with a narrowed genotype specificity.Dengue viruses (DENV) cause the most common arthropod-borne viral infection in humans worldwide, with ϳ50 million to 100 million people infected annually and ϳ2.5 billion people at risk (13, 61). Infection by four closely related but serologically distinct viruses of the Flavivirus genus (DENV serotypes 1, 2, 3, and 4 [DENV-1 to -4, respectively]) cause dengue fever (DF), an acute, self-limiting, yet severe, febrile illness, or dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS), a potentially fatal syndrome characterized by vascular leakage and a bleeding diathesis. Specific treatment or prevention of dengue disease is supportive, as there is no approved antiviral therapy or vaccine available.DENV has an ϳ11-kb, single-stranded, positive-sense RNA genome that is translated into a polyprotein and is cleaved posttranslationally into three structural (envelope [E], pre/ membrane [prM], and capsid [C]) and seven nonstructural (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) proteins. The three structural proteins encapsidate a single infectious RNA of the DENV genome, whereas the nonstructural proteins have key enzymatic or regulatory functions that promote replication. Additionally, several DENV proteins are multifunctional and modulate cell-intrinsic and cell-extrinsic host immune responses (10).Most flavivirus-neutralizing antibodies recognize the structural E protein (reviewed in reference 40). Based on X-ray crystallographic analysis (32, 33), the DENV E protein is divided into three domains: domain I (DI), which is an 8-strand...

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Section: Discussionmentioning

confidence: 99%

Genotype-Specific Neutralization and Protection by Antibodies against Dengue Virus Type 3

Brien

Austin

Sukupolvi-Petty

et al. 2010

J Virol

133

148

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“…Setting of these studies were; Thailand 6 (Zhang, C. et al 2006, Rico-Hesse R. et al 1998, Wittke,V.et al,2002, Myanmar (Thu H.M. et al,2004), India (Kukreti, H. et al,2008;Dash, P.K.et al,2006), Bangladesh (Islam, M.A.et al,2006), Sri Lanka (Kanakaratne, N. et al,2009), Taiwan (King, C.C. et al,2008) and Pakistan (Jamil B, et al 2007).…”

Section: Prisma Flow Diagrammentioning

confidence: 99%

Genetic Diversity of Dengue Virus and Associated Clinical Severity During Periodic Epidemics in South East Asia

Khan¹,

Hasan²,

Mehraj³

et al. 2012

Current Topics in Tropical Medicine

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“…The variability of DENV has permitted its classification into four antigenically different serotypes (DENV-1 to DENV-4), and the cocirculation of these four serotypes in specific geographic regions is associated with the epidemic potential of DENV [11]. This is of particular interest in Colombia, which has recorded the cocirculation of all four serotypes since 2006 [12].…”

Section: Introductionmentioning

confidence: 99%

Differential replication of dengue virus serotypes 2 and 3 in coinfections of C6/36 cells and Aedes aegypti mosquitoes

Quintero-Gil

Ospina

Osorio-Benitez

et al. 2014

J Infect Dev Ctries

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Introduction: Different dengue virus (DENV) serotypes have been associated with greater epidemic potential. In turn, the increased frequency in cases of severe forms of dengue has been associated with the cocirculation of several serotypes. Because Colombia is a country with an endemic presence of all four DENV serotypes, the aim of this study was to evaluate the in vivo and in vitro replication of the DENV-2 and DENV-3 strains under individual infection and coinfection conditions. Methodology: C6/36HT cells were infected with the two strains individually or simultaneously (coinfection). Replication capacity was evaluated by RT-qPCR, and the effects on cell viability were assessed with an MTT (3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Additionally, Aedes aegypti mosquitoes were artificially fed the two strains of each serotype individually or simultaneously. The viral genomes were quantified by RT-qPCR and the survival of the infected mosquitoes was compared to that of uninfected controls. Results: In single infections, three strains significantly affected C6/36HT cell viability, but no significant differences were found in the replication capacities of the strains of the same serotype. In the in vivo infections, mosquito survival was not affected, and no significant differences in replication between strains of the same serotype were found. Finally, in coinfections, serotype 2 replicated with a thousandfold greater efficiency than serotype 3 did both in vitro and in vivo. Conclusions: Due to the cocirculation of serotypes in endemic regions, further studies of coinfections in a natural environment would further an understanding of the transmission dynamics that affect DENV infection epidemiology.

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Comparative analysis of full genomic sequences among different genotypes of dengue virus type 3

Cited by 46 publications

References 43 publications

Genotype-Specific Neutralization and Protection by Antibodies against Dengue Virus Type 3

Genotype-Specific Neutralization and Protection by Antibodies against Dengue Virus Type 3

Genetic Diversity of Dengue Virus and Associated Clinical Severity During Periodic Epidemics in South East Asia

Differential replication of dengue virus serotypes 2 and 3 in coinfections of C6/36 cells and Aedes aegypti mosquitoes

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