scholarly journals Molecular characterization of the viral structural protein genes in the first outbreak of dengue virus type 2 in Hunan Province, inland China in 2018

2020 ◽  
Author(s):  
Jiaoqiong Guan ◽  
Zhanlong He ◽  
Meng Qin ◽  
Xialin Deng ◽  
Jun Chen ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Amino Acid ◽  
Protein Binding ◽  
Causative Agent ◽  
Binding Sites ◽  
Selection Pressure ◽  
Hunan Province ◽  
Structural Protein ◽  
Protein Binding Sites ◽  
Dengue Outbreak

Abstract Background: An unexpected dengue outbreak occurred in the Hunan Province in 2018. This is 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 investigate gene characterization, the structural protein C/prM/E genes of viruses isolated from local residents were sequenced followed by mutation and phylogenetic analysis. The recombination, selection pressure, potential secondary structure and three-dimensional structure analysis were also performed. Results: Phylogenetic analysis revealed that all epidemic strains were classified as the cosmopolitan DENV-2 genotype, closest to the Zhejiang strain (MH010629, 2017) and then Malaysia strain (KJ806803, 2013). Compared with the DENV-2SS, 151 base substitutions were found in 89 sequences of isolates, which resulted in 20 non-synonymous mutations, of which 17 mutations existed among all samples (two in capsid protein, six in prM/M, and nine in envelope proteins). Moreover, amino acid substitutions at 602th (E322:Q→H) and 670th (E390: N→S) may enhance 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 compared with DENV-2SS. Meanwhile, five changes were found in helix regions. Minor changes were observed in helical transmembrane and disordered regions. The 429th amino acid of E proteins was switch from histamine (positively charged) to asparagines (neutral) in all 89 isolate strains. No recombination events or positive selection pressure sites were observed. To our knowledge, this study is the first one to analyze the genetic characteristics of epidemic strain in the first dengue outbreak in Hunan Province, 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 to understand the intrinsic geographical relatedness of DENV-2 and contributes to further research on pathogenicity and vaccine development.

scholarly journals Molecular characterization of the viral structural protein genes in the first outbreak of dengue virus type 2 in Hunan Province, inland China in 2018

2021 ◽  
Author(s):  
Jiaoqiong Guan ◽  
Zhanlong He ◽  
Meng Qin ◽  
Xialin Deng ◽  
Jun Chen ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Amino Acid ◽  
Protein Binding ◽  
Causative Agent ◽  
Binding Sites ◽  
Selection Pressure ◽  
Hunan Province ◽  
Genetic Characteristics ◽  
Protein Binding Sites ◽  
Dengue Outbreak

Abstract 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.

scholarly journals Molecular characterization of the viral structural gene of the first dengue virus type 2 outbreak in Hunan Province, inland China

2020 ◽  
Author(s):  
Jiaoqiong Guan ◽  
Zhanlong He ◽  
Meng Qin ◽  
Xialin Deng ◽  
Jun Chen ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Amino Acid ◽  
Protein Binding ◽  
Causative Agent ◽  
Binding Sites ◽  
Selection Pressure ◽  
Tertiary Structure ◽  
Hunan Province ◽  
Protein Binding Sites ◽  
Dengue Outbreak

Abstract Background: An unexpected dengue outbreak occurred in the Hunan Province in 2018. This is the first dengue outbreak in this area of inland China resulting 172 infected. Methods: To verify the causative agent of this outbreak and investigate gene characterization, the structural protein C/prM/E genes of viruses isolated from local residents were sequenced followed by mutation, phylogenetic analysis. The recombination, selection pressure, potential secondary structure and three-dimensional structure analysis were also performed. Results: Phylogenetic analysis revealed that all epidemic strains were classified as the cosmopolitan DENV-2 genotype, closest to the Zhejiang strain (MH010629, 2017) and then Malaysia strain (KJ806803, 2013). Compared with the DENV-2SS, 151 base substitutions were found in 89 sequences of isolates, resulting in 20 nonsynonymous mutations, of which 17 mutations existed among all samples (two in capsid protein, six in prM/M, and nine in envelope proteins). Moreover, amino acid substitutions at 602 th (E322:Q→H) and 670 th (E390: N→S) may result in heightened 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 compared with DENV-2SS. Meanwhile, five changes were found in helix regions. The helical transmembrane and disordered regions have minor changes. Protein tertiary structure prediction revealed the 429 th amino acid of E proteins was switch from histamine (positively charged) to asparagines (neutral) in 89 isolate strains. No recombination events or positive selection pressure sites were detected. To our knowledge, this study is the first gene analysis of epidemic strain in the first dengue outbreak in Hunan Province, 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 understand the intrinsic geographical relatedness of DENV-2 and contributes further to research on pathogenicity and vaccine development.

scholarly journals Molecular characterization of the viral structural protein genes in the first outbreak of dengue virus type 2 in Hunan Province, inland China in 2018

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jiaoqiong Guan ◽  
Zhanlong He ◽  
Meng Qin ◽  
Xialin Deng ◽  
Jun Chen ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Amino Acid ◽  
Protein Binding ◽  
Causative Agent ◽  
Binding Sites ◽  
Selection Pressure ◽  
Hunan Province ◽  
Genetic Characteristics ◽  
Protein Binding Sites ◽  
Dengue Outbreak

Abstract 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.

A QUANTITATIVE ANALYSIS OF INTERFACIAL AMINO ACID CONSERVATION IN PROTEIN-PROTEIN HETERO COMPLEXES

2005 ◽  
Vol 03 (05) ◽  
pp. 1137-1150 ◽  
Author(s):  
BOOJALA V. B. REDDY ◽  
YIANNIS N. KAZNESSIS
Keyword(s):  
Amino Acid ◽  
Protein Binding ◽  
Binding Sites ◽  
Protein Structures ◽  
Complex Structures ◽  
Protein Surface ◽  
Protein Surfaces ◽  
Protein Binding Sites ◽  
Interaction Sites ◽  
Conserved Residue

A long-standing question in molecular biology is whether interfaces of protein-protein complexes are more conserved than the rest of the protein surfaces. Although it has been reported that conservation can be used as an indicator for predicting interaction sites on proteins, there are recent reports stating that the interface regions are only slightly more conserved than the rest of the protein surfaces, with conservation signals not being statistically significant enough for predicting protein-protein binding sites. In order to properly address these controversial reports we have studied a set of 28 well resolved hetero complex structures of proteins that consists of transient and non-transient complexes. The surface positions were classified into four conservation classes and the conservation index of the surface positions was quantitatively analyzed. The results indicate that the surface density of highly conserved positions is significantly higher in the protein-protein interface regions compared with the other regions of the protein surface. However, the average conservation index of the patches in the interface region is not significantly higher compared with other surface regions of the protein structures. This finding demonstrates that the number of conserved residue positions is a more appropriate indicator for predicting protein-protein binding sites than the average conservation index in the interacting region. We have further validated our findings on a set of 59 benchmark complex structures. Furthermore, an analysis of 19 complexes of antigen-antibody interactions shows that there is no conservation of amino acid positions in the interacting regions of these complexes, as expected, with the variable region of the immunoglobulins interacting mostly with the antigens. Interestingly, antigen interacting regions also have a higher number of non-conserved residue positions in the interacting region than the rest of the protein surface.

Amino acid preferences at protein binding sites

FEBS Letters ◽  
1994 ◽  
Vol 349 (1) ◽  
pp. 125-130 ◽  
Author(s):  
Hugo O. Villar ◽  
Lawrence M. Kauvar
Keyword(s):  
Amino Acid ◽  
Protein Binding ◽  
Binding Sites ◽  
Protein Binding Sites

scholarly journals Molecular characterization of the viral structural gene of the first dengue virus type 1 outbreak in Xishuangbanna, a border area of China, Burma and Laos

2018 ◽  
Author(s):  
Yao Lin ◽  
Dehong Ma ◽  
Songjiao Wen ◽  
Fen Zeng ◽  
Shan Hong ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Dengue Virus ◽  
Molecular Clock ◽  
Binding Sites ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Structural Protein ◽  
Serum Samples ◽  
Protein Binding Sites ◽  
Border City

AbstractIn the context of recent arbovirus epidemics, dengue fever is becoming a greater concern around the world. In August 2017, Xishuangbanna, which is a border city of China, Burma and Laos, had its first major dengue outbreak. A total of 156 serum samples from febrile patients were collected; 97 DENV positive serum samples were screened out, and viral RNAs were successfully and directly extracted, including 77 cases from China and 20 cases from Myanmar. Phylogenetic analysis revealed that all of the strains were classified as DENV-1. There are eight epidemic dengue strains from Myanmar and 74 from Jinghong, Xishuangbanna, that were classified as cluster 1, which are the most similar to the strain of China Guangzhou 2011. There are three epidemic strains from Xishuangbanna Mengla that were classified as cluster 2, which have the closest relationship to the strain of China Hubei 2014. However, there are 12 epidemic strains from Myanmar that were classified as cluster 3, which have the closest relationship to the strain of Laos from 2008, which shows that there is a recycling epidemic trend of DENV in China. There were 236 mutations in the base, which caused 31 nonsynonymous mutations in the DENV structural protein C/prM/E genes when the strain of Xishuangbanna and Myanmar were compared with the DENV-1SS. There is no clear homologous recombination signal among these stains. Homology modeling possibly predicted a three-dimensional structure of the structural protein of these strains and revealed that they had the same three-dimensional structure and all had five predicted protein binding sites, but there are differences in binding site 434 (DENV-1SS: Thr434, DV-Jinghong: Ser434, DV-Myanmar: Ser434, DV-Mengla: Ser434). The results of the molecular clock phylogenetic and demographic reconstruction analysis show that DENV-1 became highly diversified in 1972 followed by a slightly decreased period until 2017. In conclusion, our study lays the foundation for studying the global evolution and prevalence of DENV.Author SummaryDengue fever (DF) is a mosquito-borne illness caused by a flavivirus. Human infections with Dengue virus (DENV) could cause fever, cutaneous rash and malaise. Xishuangbanna, which is located in the southwestern Yunnan Province and is a border city with China, Burma and Laos, was reported to have outbreak of DENV in 2013 and 2015 with different types. However, there was a large outburst of dengue in May 2017. To understand the genetic characterization, potential source and evolution of the virus, 156 serum samples were analyzed. We focused on: (i) Phylogenetic analysis of the structural protein genes sequences; (ii) Mutation, recombination analysis and predicted protein binding sites of the structural protein genes; (iii) Molecular clock and demographic reconstruction of global dengue virus serotype 1(DENV-1). Our results indicated that this is the first outbreak of DENV-1 in Xishuangbanna, dengue epidemic strains on the Burma border of China show diversification, we found a virulence site changed from I to T(amino acid position: 440), which may lead to weakened virulence of the epidemic strains. We found that the evolution of DENV-1 is dominated by regional evolution. What’s more, DENV-1 became highly diversified in 1972 followed by a slightly decreased period until 2017.

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