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Metabolic Processes Are Differentially Regulated During Wild-Type and Attenuated Dengue Virus Infection in Aedes aegypti

Tanamas SiriphanitchakornProgramme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore;
Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore;

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Cassandra M. ModahlDepartment of Biological Sciences, Faculty of Science, National University of Singapore, Singapore;

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R. Manjunatha KiniDepartment of Biological Sciences, Faculty of Science, National University of Singapore, Singapore;
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore;

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Eng Eong OoiProgramme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore;
Saw Swee Hock School of Public Health, National University of Singapore, Singapore;
Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

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Milly M. ChoyProgramme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore;

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ABSTRACT.

Successful completion of the dengue virus (DENV) life cycle in its mosquito vectors is important for efficient human–mosquito–human cycle of transmission, but the virus–mosquito interactions that underpin this critical event are poorly defined. To understand the virus–host interactions that determine viral infection by Aedes aegypti, the principal DENV vector, the authors compared transcriptomic changes in the head/thorax of the mosquito after intrathoracic infection with the wild-type DENV2 16681 strain and its attenuated derivative, PDK53. Using high-throughput RNA-sequencing, the authors identified 1,629 differentially expressed genes (DEGs) during 16681 infection, compared with only 22 DEGs identified during PDK53 infection, indicating that 16681 infection triggers a more robust host transcriptomic response compared with PDK53 infection. The authors further found that 16681 infection, but not PDK53 infection, altered metabolism in these heads/thoraces. Altogether, our findings reveal differential regulation of metabolic processes during wild-type and attenuated DENV infection, and suggest the need for future work to study the role of metabolic processes in determining DENV infection and replication in its mosquito vectors.

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Author Notes

Address correspondence to Milly M. Choy, Programme in Emerging Infectious Diseases, Duke-NUS Medical School, 169857, Singapore. E-mail: milly.choy@duke-nus.edu.sg

Financial support: This work was funded by the Ministry of Education Tier 3 Grant (Singapore) and the Open Fund-Young Individual Research Grant administered by the National Medical Research Council of Singapore.

Disclosure: Eng Eong Ooi served as a dengue vaccine advisory board member for Takeda Vaccines, which uses DENV2 PDK53 strain as a component of their dengue vaccine candidate, TAK-003.

Authors’ addresses: Tanamas Siriphanitchakorn, Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, and Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore, E-mail: t.siriphanitchakorn@u.nus.edu. Cassandra M. Modahl, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, United Kingdom, E-mail: cassandra.modahl@lstmed.ac.uk. R. Manjunatha Kini, Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore, and Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, E-mail: dbskinim@nus.edu.sg. Eng Eong Ooi, Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Saw Swee Hock School of Public Health, National University of Singapore, Singapore, and Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, E-mail: engeong.ooi@duke-nus.edu.sg. Milly M. Choy, Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, E-mail: milly.choy@duke-nus.edu.sg.

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