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Comparison of full-length genomics sequences between dengue virus serotype 3, parental strain, and its derivatives, and B-cell epitopes prediction from envelope region.

ABSTRACT: Biological markers are normally used to evaluate the candidate of live-attenuated dengue vaccines. D3V 16562 Vero 23 and D3V 16562 Vero 33 which were derivatives of D3V 16562, parental strain, showed the similar biological data. We used molecular techniques and computational tools to evaluate these derivatives. The nucleotide and amino acid sequences of the derivatives were compared to their parent. The secondary structures of untranslated regions and B-cell epitopes were predicted. The results showed that nucleotide substitutions mostly occurred in NS5 and NS5 of V2 was unusual because of amino acid change at 3349 (tryptophan ?stop codon). The nucleotide substitutions in 5'UTR, prM, E, NS1, NS2A, NS3, and 3'UTR were 4, 1, 2, 2, 1, 3, and 2, respectively. The secondary structure of 5'UTR of V2 was different from P and V1. The secondary structure of 3'UTR of V2 was similar to P and certainly distinct from V1. Furthermore, B-cell epitopes prediction revealed that there were 21 epitopes of envelope and the interesting epitope was at position 297-309 because it was in domain III in which the neutralizing antibody is induced. For this study, the attenuation of derivatives was caused by the nucleotide substitutions in 5'UTR, 3'UTR, and NS5 regions. The genotypic data and B-cell epitope make the derivatives attractive for the chimeric and peptide DENV vaccine development.

SUBMITTER: Thaisonthi S

PROVIDER: S-EPMC3725003 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Comparison of full-length genomics sequences between dengue virus serotype 3, parental strain, and its derivatives, and B-cell epitopes prediction from envelope region.

Thaisonthi Siriwattana S Rabablert Jundee J Yoksan Sutee S

Bioinformation 20130712 12

Biological markers are normally used to evaluate the candidate of live-attenuated dengue vaccines. D3V 16562 Vero 23 and D3V 16562 Vero 33 which were derivatives of D3V 16562, parental strain, showed the similar biological data. We used molecular techniques and computational tools to evaluate these derivatives. The nucleotide and amino acid sequences of the derivatives were compared to their parent. The secondary structures of untranslated regions and B-cell epitopes were predicted. The results ...[more]

PMID: 23904739

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Project description:IntroductionDengue hemorrhagic fever is caused by four serotypes of dengue viruses transmitted by mosquitoes. In Vietnam, dengue outbreaks occur every year, and all four serotypes have been found circulating with the dominant one varying over time. However, in 2017 an unusual dengue fever outbreak occurred in the North of Vietnam, predominantly caused by DENV1 (92%) and DENV2 (7.3%). The objective of the present study was to obtain and characterize the full-length genome sequence of seven DENV2 strains in 2017 epidemic.Materials and methodsWhole-genome sequencing of seven DENV2 isolates from the 2017 outbreak were obtained using the Illumina MiSeq next generation sequencer system. Complete genome sequences were then analyzed to find out genetic variants and genetic relationships between these DENV2 with other strains that circulated in Vietnam previously and other regions of the world.ResultsThe complete genome sequence of seven DENV2 isolates in the 2017 dengue outbreak comprised 10,696 nucleotides with an open reading frame coding for 3392 amino acids. The genome analysis showed only a small number of amino acid changes which were obtained in all genes, in which a few amino acids substitutions were distributed over the positions such as G156 (NS1), V106 (NS2A), and L258/T260 (NS5). The phylogenetic analysis revealed that the DENV2 isolates in the 2017 outbreak were most closely related to the dengue virus from India in 2006, suggesting that the causative virus originated from the DENV2 that caused dengue hemorrhagic fever in 2006 in India.ConclusionThe first complete genome sequences of seven DENV2 isolates in the 2017 dengue outbreak in Northern Vietnam were successfully obtained. The genetic and phylogenetic data indicated that these DENV2 isolates were not causative virus circulating in Vietnam previously but originated from India in 2006. These data are emerging and providing valuable information for the management and surveillance of dengue in Vietnam.

Project description:The DENV envelope (E) and pre-membrane (prM) glycoproteins are primary targets of serologic immunity after infection and vaccination. Of these, serotype-specific (TS) antibodies typically target E domains, while serotype cross-reactive (CR) antibodies typically the target prM protein and conserved E regions. To identify and quantify E-domain TS neutralizing antibody responses in polyclonal sera, we developed a panel of chimeric DENV4/2 viruses that incorporate DENV2 envelope domain I, II, and III (DENV4/2-EDI, EDII, EDIII) into the DENV4 E glycoprotein. Chimeric DENV4/2 viruses were recovered, replicated efficiently, and displayed similar maturation states as parental viruses. The recovery of viable DENV4/2-EDII recombinants required the inclusion of chimeric DENV4/2 prM that maintained critical interactions with chimeric E. To assess structural integrity and epitope display of chimeric viruses, we examined neutralization of mature virions by monoclonal antibodies (mAbs) and heterotypic polyclonal sera. The ED-chimeric virions preserved epitopes of TS and envelope-dimer-epitope CR mAbs and had similar sensitivity to CR polyclonal responses as parental strains. Primary sera from natural infection and human challenge target a region centered on EDIII and secondarily target EDII and EDI. Sera from natural infection had a unique neutralization pattern compared to sera from human challenge, which included greater frequency and higher titer of responses against DENV EDII. In summary, DENV4/2 E recombinant viruses delineate the subdomain targets of TS antibodies after vaccination and primary infection, which may provide new correlates of protection or identify epitopes of neutralizing monoclonal antibodies.IMPORTANCEThe four dengue virus (DENV) serotypes infect several hundred million people each year. Although primary infection is generally mild, subsequent infection by differing serotypes increases the risk for symptomatic disease ranging from fever to life-threatening shock. Despite the availability of licensed vaccines, a comprehensive understanding of antibodies that target the viral envelope protein and protect from infection remains incomplete. In this manuscript, we develop a panel of recombinant viruses that graft each envelope domain of DENV2 onto the DENV4 envelope glycoprotein, revealing protein interactions important for virus viability. Furthermore, we map neutralizing antibody responses after primary DENV2 natural infection and a human challenge model to distinct domains on the viral envelope protein. The panel of recombinant viruses provides a new tool for dissecting the E domain-specific targeting of protective antibody responses, informing future DENV vaccine design.

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Comparison of full-length genomics sequences between dengue virus serotype 3, parental strain, and its derivatives, and B-cell epitopes prediction from envelope region.

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Comparison of full-length genomics sequences between dengue virus serotype 3, parental strain, and its derivatives, and B-cell epitopes prediction from envelope region.

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