Immunogenicity of a Candidate DNA Vaccine Based on the &lt;i&gt;prM/E&lt;/i&gt; Genes of a Dengue Type 2 Virus Cosmopolitan Genotype Strain

Putri, Dwi Hilda; Sudiro, Tjahjani Mirawati; Yunita, Rina; Jaya, Ungke Anton; Dewi, Beti Ernawati; Sjatha, Fithriyah; Konishi, Eiji; Hotta, Hak; Sudarmono, Pratiwi

doi:10.7883/yoken.jjid.2014.313

Cited by 8 publications

(6 citation statements)

References 29 publications

(37 reference statements)

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“…A cell culture-adapted HCV variant (JFH1 strain of genotype 2a) was propagated as described previously (27,28). An Indonesian strain of dengue virus type 2 (DENV, DS-18/09 strain) was propagated in mosquito-derived C6/36 cells and African green monkey kidney-derived Vero cells as described previously (29,30).…”

Section: Cells and Virusesmentioning

confidence: 99%

Anti-Hepatitis C Virus Activity of a Crude Extract from Longan (<i>Dimocarpus longan</i> Lour.) Leaves

et al. 2016

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SUMMARY:Infection with hepatitis C virus (HCV) results in hepatitis C, a disease characterized by chronic infection, cirrhosis, and hepatocellular carcinoma. Currently, the standard therapy is a combination of pegylated interferon-a plus ribavirin with NS3 protease inhibitors. Addition of NS3 protease inhibitors to the standard therapy improves response rates; however, use of NS3 protease inhibitors is also associated with significant adverse effects and an increase in the overall cost of treatment. Therefore, there is a need to develop safe and inexpensive drugs for the treatment of HCV infections. In this study, we examined the antiviral activity of a crude extract from Dimocarpus longan leaves against HCV (genotype 2a strain JFH1). The D. longan crude extract (DL-CE) exhibited anti-HCV activity with a 50z effective concentration (EC 50 ) of 19.4 mg/ml without cytotoxicity. A time-of-addition study demonstrated that DL-CE has anti-HCV activity at both the entry and post-entry steps and markedly blocks the viral entry step through direct virucidal activity with marginal inhibition of virion assembly. Co-treatment of DL-CE with cyclosporine A, an immunosuppressant or telaprevir, an NS3 protease inhibitor, resulted in additive and synergistic antiviral effects, respectively. Our findings suggest that DL-CE may be useful as an add-on therapy candidate for treating HCV infections.

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Section: Cells and Virusesmentioning

confidence: 99%

Anti-Hepatitis C Virus Activity of a Crude Extract from Longan (<i>Dimocarpus longan</i> Lour.) Leaves

et al. 2016

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“…DENV is categorized into four serotypes (DENV-1–4) based on genetic and antigenic characteristics. The inter-serotype nucleotide variability is ~ 30% 4 , 5 . Each serotype is genetically sub-divided into genotypes 6 , 7 .…”

Section: Introductionmentioning

confidence: 99%

Evolution, heterogeneity and global dispersal of cosmopolitan genotype of Dengue virus type 2

Yenamandra

Koo

Chiang

et al. 2021

Sci Rep

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Dengue virus type 2 (DENV-2) contributes substantially to the dengue burden and dengue-related mortality in the tropics and sub-tropics. DENV-2 includes six genotypes, among which cosmopolitan genotype is the most widespread. The present study investigated the evolution, intra-genotype heterogeneity and dispersal of cosmopolitan genotype to understand unique genetic characteristics that have shaped the molecular epidemiology and distribution of cosmopolitan lineages. The spatial analysis demonstrated a wide geo-distribution of cosmopolitan genotype through an extensive inter-continental network, anchored in Southeast Asia and Indian sub-continent. Intra-genotype analyses using 3367 envelope gene sequences revealed six distinct lineages within the cosmopolitan genotype, namely the Indian sub-continent lineage and five other lineages. Indian sub-continent lineage was the most diverged among six lineages and has almost reached the nucleotide divergence threshold of 6% within E gene to qualify as a separate genotype. Genome wide amino acid signatures and selection pressure analyses further suggested differences in evolutionary characteristics between the Indian sub-continent lineage and other lineages. The present study narrates a comprehensive genomic analysis of cosmopolitan genotype and presents notable genetic characteristics that occurred during its evolution and global expansion. Whether those characteristics conferred a fitness advantage to cosmopolitan genotype in different geographies warrant further investigations.

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“…prM contains a furin cleavage site that is cleaved into C‐terminal M protein and N‐terminal pr protein, resulting in the formation of a mature infectious virus 17,18 . Cells infected with DENV secrete a heterogeneous mixture of virus particles that vary as a result of the inefficient cleavage of prM to M by furin during DENV maturation, ranging from fully mature (containing M) and partially mature (containing prM and M) to fully immature (containing prM) virions 19,20 …”

Section: Introductionmentioning

confidence: 99%

“…17,18 Cells infected with DENV secrete a heterogeneous mixture of virus particles that vary as a result of the inefficient cleavage of prM to M by furin during DENV maturation, ranging from fully mature (containing M) and partially mature (containing prM and M) to fully immature (containing prM) virions. 19,20 Recent studies have indicated that the prM protein is related to ADE of DENV, suggesting the potential role of prM-specific monoclonal antibodies in enhancing DENV infection. prM protein is a major target of the humoral immune response to DENV.…”

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confidence: 99%

Antibody‐dependent enhancement (ADE) of dengue virus: Identification of the key amino acid that is vital in DENV vaccine research

Cui

Wang

et al. 2021

The Journal of Gene Medicine

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Background The antibody‐dependent enhancement (ADE) of dengue virus (DENV) has critically restricted vaccine development. Prior research suggested pr4 as the probable ADE epitope of DENV. Methods Chimeric DENV was constructed by replacing the DENV pr4 gene with the corresponding Japanese encephalitis virus (JEV) gene to determine whether it can reduce ADE activities. An alanine scanning method and bioinformatics analysis were utilized to identify the amino acid of pr4 that was crucial as an ADE epitope. Results Chimeric virus reduced ADE and virulence. The amino acids at the following locations on the mutant peptides showed significantly reduced binding ability to prM antibody: pr4.5 (position 5 – leucine), pr4.6 (position 6 – leucine), pr4.7 (position 7 – phenyalanine) and pr4.16 (position 16 – cysteine). The four amino acids had formed a pocket‐like structure, which could increase the possibility of binding to an antibody. Conclusions ADE activities could be reduced by replacing the DENV pr4 gene with the corresponding JEV gene. Leucine at position 5, leucine at position 6, phenyalanine at position 7 and cysteine at position 16 were the key amino acid sites in the ADE response of DENV. The occurrence of ADE can potentially be reduced by the replacement of key amino acids, hence highlighting its possible contribution to dengue vaccine design, paving a way for future vaccine research.

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Immunogenicity of a Candidate DNA Vaccine Based on the <i>prM/E</i> Genes of a Dengue Type 2 Virus Cosmopolitan Genotype Strain

Cited by 8 publications

References 29 publications

Anti-Hepatitis C Virus Activity of a Crude Extract from Longan (<i>Dimocarpus longan</i> Lour.) Leaves

Anti-Hepatitis C Virus Activity of a Crude Extract from Longan (<i>Dimocarpus longan</i> Lour.) Leaves

Evolution, heterogeneity and global dispersal of cosmopolitan genotype of Dengue virus type 2

Antibody‐dependent enhancement (ADE) of dengue virus: Identification of the key amino acid that is vital in DENV vaccine research

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