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Infectivity of Dengue Virus Serotypes 1 and 2 is Correlated to E Protein Intrinsic Dynamics But Not to Envelope Conformations

42 Pages Posted: 11 Jun 2018 Publication Status: Published

See all articles by Kamal Kant Sharma

Kamal Kant Sharma

National University of Singapore (NUS) - Department of Biological Sciences

Xin-Xiang Lim

National University of Singapore (NUS) - Department of Biological Sciences

Sarala Neomi Tantirimudalige

National University of Singapore (NUS) - Department of Biological Sciences

Anjali Gupta

National University of Singapore (NUS) - Department of Biological Sciences

Jan K. Marzinek

National University of Singapore (NUS) - Department of Biological Sciences; Agency for Science, Technology and Research (A*STAR) - Bioinformatics Institute

Daniel Holdbrook

National University of Singapore (NUS) - Department of Biological Sciences; Agency for Science, Technology and Research (A*STAR) - Bioinformatics Institute

Xin Ying Elisa Lim

Duke-NUS Graduate Medical School Singapore

Peter J. Bond

National University of Singapore (NUS) - Department of Biological Sciences

Ganesh S. Anand

National University of Singapore (NUS) - Department of Biological Sciences

Thorsten Wohland

National University of Singapore (NUS) - Department of Biological Sciences

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Abstract

Dengue is a mosquito-borne virus with dire health and economic impact. Dengue is responsible for an estimated ~390 million infections per year, with Dengue 2 (DENV2) being the most virulent strain among the four serotypes. Interestingly, it is also for strains of this serotype that temperature-dependent large scale morphological changes, termed as “breathing”, have been observed. Although, the structure of these morphologies has been solved to 3.5 Å resolution, the dynamics of the viral envelope are unknown. Here, we combine fluorescence and mass spectrometry and molecular dynamics simulations to provide insights into DENV2 structural dynamics in comparison to DENV1. We observe hitherto unseen conformational changes and structural dynamics of the DENV2 envelope that are influenced by both temperature and divalent cations. Our results show that for DENV2 and DENV1 the intrinsic dynamics but not the specific morphologies are correlated to viral infectivity.

Suggested Citation

sharma, kamal kant and Lim, Xin-Xiang and Tantirimudalige, Sarala Neomi and Gupta, Anjali and Marzinek, Jan K. and Holdbrook, Daniel and Lim, Xin Ying Elisa and Bond, Peter J. and Anand, Ganesh S. and Wohland, Thorsten, Infectivity of Dengue Virus Serotypes 1 and 2 is Correlated to E Protein Intrinsic Dynamics But Not to Envelope Conformations (June 2018). Available at SSRN: https://ssrn.com/abstract=3193413 or http://dx.doi.org/10.2139/ssrn.3193413
This version of the paper has not been formally peer reviewed.

Kamal kant Sharma (Contact Author)

National University of Singapore (NUS) - Department of Biological Sciences ( email )

14 Science Drive 4
Singapore, 117543
China

Xin-Xiang Lim

National University of Singapore (NUS) - Department of Biological Sciences

Bukit Timah Road 469 G
Singapore, 117591
Singapore

Sarala Neomi Tantirimudalige

National University of Singapore (NUS) - Department of Biological Sciences

14 Science Drive 4
Singapore, 117543
China

Anjali Gupta

National University of Singapore (NUS) - Department of Biological Sciences

14 Science Drive 4
Singapore, 117543
China

Jan K. Marzinek

National University of Singapore (NUS) - Department of Biological Sciences

14 Science Drive 4
Singapore, 117543
China

Agency for Science, Technology and Research (A*STAR) - Bioinformatics Institute

30 Biopolis Street
#07-01 Matrix
Singapore, 138671
China

Daniel Holdbrook

National University of Singapore (NUS) - Department of Biological Sciences

14 Science Drive 4
Singapore, 117543
China

Agency for Science, Technology and Research (A*STAR) - Bioinformatics Institute

30 Biopolis Street
#07-01 Matrix
Singapore, 138671
China

Xin Ying Elisa Lim

Duke-NUS Graduate Medical School Singapore

Singapore
Singapore

Peter J. Bond

National University of Singapore (NUS) - Department of Biological Sciences

14 Science Drive 4
Singapore, 117543
China

Ganesh S. Anand

National University of Singapore (NUS) - Department of Biological Sciences ( email )

Bukit Timah Road 469 G
Singapore, 117591
Singapore

Thorsten Wohland

National University of Singapore (NUS) - Department of Biological Sciences ( email )

14 Science Drive 4
Singapore, 117543
China