Molecular modelling analysis of T219A mutant envelope protein revealed novel virulence enhancing factors in Dengue virus isolated from Kerala state, India
| Autor: | Kasinathan Gunasekaran, P. Jambulingam, N. Pradeep Kumar, G. Jeyakodi, Y. Nanda Kumar |
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| Rok vydání: | 2020 |
| Předmět: |
Virulence Factors
viruses Mutant Virulence India Health Informatics Biology Dengue virus medicine.disease_cause Antibodies Viral 030218 nuclear medicine & medical imaging Dengue 03 medical and health sciences 0302 clinical medicine Viral Envelope Proteins medicine Humans Receptor chemistry.chemical_classification Mutation Wild type virus diseases Lipid bilayer fusion Dengue Virus Virology Computer Science Applications chemistry Mutant Proteins Glycoprotein 030217 neurology & neurosurgery Software |
| Zdroj: | Computer methods and programs in biomedicine. 195 |
| ISSN: | 1872-7565 |
| Popis: | Dengue virus (DENV) is an emerging health threat and its envelope glycoprotein E, is involved in the anchoring and fusion mechanisms. Anchoring followed by conformational changes of E-protein are responsible for the fusion and entry of DENV into host. The variation in the conformation of the E-protein due to mutations, results in its altered binding with antibodies (Abs) and also its receptors. This leads to failure of neutralization of DENV and enhance the infection. In our earlier studies we have identified T219A mutation in the E-protein of DENV and the present study is focused on the impact of this mutation on the conformation of E-protein and also its binding variation with Abs and Fc-γ receptor. A comparative molecular modelling studies of wild type and T219A mutant E-proteins revealed that, the mutation induced several conformational variations in the E-protein and resulted in the variable binding orientation with altered affinities. Further, the mutation was also observed to enhance the fusion mechanism by Fc-γ receptors that mediate the efficient entry of DENV into host cell through altered membrane fusion mechanism. Such conformational variations of E-protein could be the responsible factors for enhanced virulence of DENV infections. |
| Databáze: | OpenAIRE |
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