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Research article
Qiangming sun
Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Medical Biology
Corresponding Author
ORCiD: https://orcid.org/0000-0002-6786-049X
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: An unexpected dengue outbreak occurred in Hunan Province in 2018. This was the first dengue outbreak in this area of inland China, and 172 cases were reported.
Methods: To verify the causative agent of this outbreak and characterise the viral genes, the genes encoding the structural proteins C/prM/E of viruses isolated from local residents were sequenced followed by mutation and phylogenetic analysis. Recombination, selection pressure, potential secondary structure and three-dimensional structure analyses were also performed.
Results: Phylogenetic analysis revealed that all epidemic strains were of the cosmopolitan DENV-2 genotype and were most closely related to the Zhejiang strain (MH010629, 2017) and then the Malaysia strain (KJ806803, 2013). Compared with the sequence of DENV-2SS, 151 base substitutions were found in the sequences of 89 isolates; these substitutions resulted in 20 non-synonymous mutations, of which 17 mutations existed in all samples (two in the capsid protein, six in the prM/M proteins, and nine in the envelope proteins). Moreover, amino acid substitutions at the 602nd (E322:Q→H) and 670th (E390: N→S) amino acids may have enhanced the virulence of the epidemic strains. One new DNA binding site and five new protein binding sites were observed. Two polynucleotide binding sites and seven protein binding sites were lost in the epidemic strains compared with DENV-2SS. Meanwhile, five changes were found in helical regions. Minor changes were observed in helical transmembrane and disordered regions. The 429th amino acid of the E protein switched from a histamine (positively charged) to an asparagine (neutral) in all 89 isolated strains. No recombination events or positive selection pressure sites were observed. To our knowledge, this study is the first to analyse the genetic characteristics of epidemic strains in the first dengue outbreak in Hunan Province in inland China.
Conclusions: The causative agent is likely to come from Zhejiang Province, a neighbouring province where dengue fever broke out in 2017. This study may help clarify the intrinsic geographical relatedness of DENV-2 and contribute to further research on pathogenicity and vaccine development.
Keywords
Dengue virus, structural protein, phylogenetic trees, protein structure, selection pressure
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View the published article at BMC Infectious Diseases.
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On 06 Dec, 2020
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Received 01 Dec, 2020
Reviewer #1 agreed
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Reviewers invited
Invitations sent on 10 Nov, 2020
Editor assigned
On 01 Nov, 2020
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On 02 Oct, 2020
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Reviewer #2 agreed
On 10 Sep, 2020
Review #1 received
Received 15 Jun, 2020
Reviewer #1 agreed
On 25 May, 2020
Reviewers invited
Invitations sent on 24 Jan, 2020
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On 09 Jan, 2020
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See the published version of this preprint at BMC Infectious Diseases.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Qiangming sun
Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Medical Biology
Corresponding Author
ORCiD: https://orcid.org/0000-0002-6786-049X
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at BMC Infectious Diseases.
Version 3
Posted 14 Jan, 2021
No community comments so far
Editorial decision: Minor revision
On 13 Jan, 2021
Editor assigned
On 04 Jan, 2021
Submission checks complete
On 04 Jan, 2021
Editor invited
On 04 Jan, 2021
No comments provided
Editorial decision: Major revision
On 06 Dec, 2020
Review #1 received
Received 01 Dec, 2020
Reviewer #1 agreed
On 11 Nov, 2020
Reviewers invited
Invitations sent on 10 Nov, 2020
Editor assigned
On 01 Nov, 2020
Submission checks complete
On 01 Nov, 2020
Editor invited
On 01 Nov, 2020
No comments provided
Editorial decision: Major revision
On 02 Oct, 2020
Review #2 received
Received 30 Sep, 2020
Reviewer #2 agreed
On 10 Sep, 2020
Review #1 received
Received 15 Jun, 2020
Reviewer #1 agreed
On 25 May, 2020
Reviewers invited
Invitations sent on 24 Jan, 2020
Editor assigned
On 09 Jan, 2020
First submitted
On 08 Jan, 2020
Submission checks complete
On 08 Jan, 2020
Editor invited
On 08 Jan, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at BMC Infectious Diseases.
Background: An unexpected dengue outbreak occurred in Hunan Province in 2018. This was the first dengue outbreak in this area of inland China, and 172 cases were reported.
Methods: To verify the causative agent of this outbreak and characterise the viral genes, the genes encoding the structural proteins C/prM/E of viruses isolated from local residents were sequenced followed by mutation and phylogenetic analysis. Recombination, selection pressure, potential secondary structure and three-dimensional structure analyses were also performed.
Results: Phylogenetic analysis revealed that all epidemic strains were of the cosmopolitan DENV-2 genotype and were most closely related to the Zhejiang strain (MH010629, 2017) and then the Malaysia strain (KJ806803, 2013). Compared with the sequence of DENV-2SS, 151 base substitutions were found in the sequences of 89 isolates; these substitutions resulted in 20 non-synonymous mutations, of which 17 mutations existed in all samples (two in the capsid protein, six in the prM/M proteins, and nine in the envelope proteins). Moreover, amino acid substitutions at the 602nd (E322:Q→H) and 670th (E390: N→S) amino acids may have enhanced the virulence of the epidemic strains. One new DNA binding site and five new protein binding sites were observed. Two polynucleotide binding sites and seven protein binding sites were lost in the epidemic strains compared with DENV-2SS. Meanwhile, five changes were found in helical regions. Minor changes were observed in helical transmembrane and disordered regions. The 429th amino acid of the E protein switched from a histamine (positively charged) to an asparagine (neutral) in all 89 isolated strains. No recombination events or positive selection pressure sites were observed. To our knowledge, this study is the first to analyse the genetic characteristics of epidemic strains in the first dengue outbreak in Hunan Province in inland China.
Conclusions: The causative agent is likely to come from Zhejiang Province, a neighbouring province where dengue fever broke out in 2017. This study may help clarify the intrinsic geographical relatedness of DENV-2 and contribute to further research on pathogenicity and vaccine development.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
This is a list of supplementary files associated with this preprint. Click to download.
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