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Bhatt S et al.2013. The global distribution and burden of dengue. Nature 496: 504–507.
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2.
Salazar MI, Richardson JH, Sanchez-Vargas I, Olson KE, Beaty BJ , 2007. Dengue virus type 2: replication and tropisms in orally infected Aedes aegypti mosquitoes. BMC Microbiol 7: 9.
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3.
Pompon J et al.2017. Dengue subgenomic flaviviral RNA disrupts immunity in mosquito salivary glands to increase virus transmission. PLoS Pathog 13: e1006535.
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Choy MM et al., 2020. A non-structural 1 protein G53D substitution attenuates a clinically tested live dengue vaccine. Cell Rep 31: 107617.
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Butrapet S, Huang CY, Pierro DJ, Bhamarapravati N, Gubler DJ, Kinney RM , 2000. Attenuation markers of a candidate dengue type 2 vaccine virus, strain 16681 (PDK-53), are defined by mutations in the 5' noncoding region and nonstructural proteins 1 and 3. J Virol 74: 3011–3019.
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Choy MM, Sessions OM, Gubler DJ, Ooi EE , 2015. Production of infectious dengue virus in Aedes aegypti is dependent on the ubiquitin proteasome pathway. PLoS Negl Trop Dis 9: e0004227.
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Chowdhury A, Modahl CM, Tan ST, Wong Wei Xiang B, Misse D, Vial T, Kini RM, Pompon JF , 2020. JNK pathway restricts DENV2, ZIKV and CHIKV infection by activating complement and apoptosis in mosquito salivary glands. PLoS Pathog 16: e1008754.
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Metabolic Processes Are Differentially Regulated During Wild-Type and Attenuated Dengue Virus Infection in Aedes aegypti
Tanamas Siriphanitchakorn
Tanamas Siriphanitchakorn
Programme 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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Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore;
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Cassandra M. Modahl
Cassandra M. Modahl
Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore;
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R. Manjunatha Kini
R. Manjunatha Kini
Department 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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Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore;
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Eng Eong Ooi
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;
Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
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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. Choy
Milly M. Choy
Programme 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
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.
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Bhatt S et al.2013. The global distribution and burden of dengue. Nature 496: 504–507.
-
2.
Salazar MI, Richardson JH, Sanchez-Vargas I, Olson KE, Beaty BJ , 2007. Dengue virus type 2: replication and tropisms in orally infected Aedes aegypti mosquitoes. BMC Microbiol 7: 9.
-
3.
Pompon J et al.2017. Dengue subgenomic flaviviral RNA disrupts immunity in mosquito salivary glands to increase virus transmission. PLoS Pathog 13: e1006535.
-
4.
Choy MM et al., 2020. A non-structural 1 protein G53D substitution attenuates a clinically tested live dengue vaccine. Cell Rep 31: 107617.
-
5.
Khin MM, Jirakanjanakit N, Yoksan S, Bhamarapravati N , 1994. Infection, dissemination, transmission, and biological attributes of dengue-2 PDK53 candidate vaccine virus after oral infection in Aedes aegypti. Am J Trop Med Hyg 51: 864–869.
-
6.
Butrapet S, Huang CY, Pierro DJ, Bhamarapravati N, Gubler DJ, Kinney RM , 2000. Attenuation markers of a candidate dengue type 2 vaccine virus, strain 16681 (PDK-53), are defined by mutations in the 5' noncoding region and nonstructural proteins 1 and 3. J Virol 74: 3011–3019.
-
7.
Franz AW, Kantor AM, Passarelli AL, Clem RJ , 2015. Tissue barriers to arbovirus infection in mosquitoes. Viruses 7: 3741–3767.
-
8.
Choy MM, Sessions OM, Gubler DJ, Ooi EE , 2015. Production of infectious dengue virus in Aedes aegypti is dependent on the ubiquitin proteasome pathway. PLoS Negl Trop Dis 9: e0004227.
-
9.
Chowdhury A, Modahl CM, Tan ST, Wong Wei Xiang B, Misse D, Vial T, Kini RM, Pompon JF , 2020. JNK pathway restricts DENV2, ZIKV and CHIKV infection by activating complement and apoptosis in mosquito salivary glands. PLoS Pathog 16: e1008754.
-
10.
Giraldo-Calderon GI et al.2015. VectorBase: an updated bioinformatics resource for invertebrate vectors and other organisms related with human diseases. Nucleic Acids Res 43: D707–D713.
-
11.
Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, Batut P, Chaisson M, Gingeras TR , 2013. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29: 15–21.
-
12.
Conesa A, Gotz S, Garcia-Gomez JM, Terol J, Talon M, Robles M , 2005. Blast2GO: a universal tool for annotation, visualization and analysis in functional genomics research. Bioinformatics 21: 3674–3676.
-
13.
Kanehisa M, Goto S , 2000. KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res 28: 27–30.
-
14.
Huerta-Cepas J et al.2019. eggNOG 5.0: a hierarchical, functionally and phylogenetically annotated orthology resource based on 5090 organisms and 2502 viruses. Nucleic Acids Res 47: D309–D314.
-
15.
Gramates LS et al.2017. FlyBase at 25: looking to the future. Nucleic Acids Res 45: D663–D671.
-
16.
Xi Z, Ramirez JL, Dimopoulos G , 2008. The Aedes aegypti toll pathway controls dengue virus infection. PLoS Pathog 4: e1000098.
-
17.
Behura SK, Gomez-Machorro C, Harker BW, deBruyn B, Lovin DD, Hemme RR, Mori A, Romero-Severson J, Severson DW , 2011. Global cross-talk of genes of the mosquito Aedes aegypti in response to dengue virus infection. PLoS Negl Trop Dis 5: e1385.
-
18.
Colpitts TM, Cox J, Vanlandingham DL, Feitosa FM, Cheng G, Kurscheid S, Wang P, Krishnan MN, Higgs S, Fikrig E , 2011. Alterations in the Aedes aegypti transcriptome during infection with West Nile, dengue and yellow fever viruses. PLoS Pathog 7: e1002189.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 13283 | 1199 | 63 |
| Full Text Views | 223 | 24 | 1 |
| PDF Downloads | 77 | 13 | 2 |