國家衛生研究院 NHRI:Item 3990099045/15913

NHRI > National Institute of Infectious Diseases and Vaccinology > Chun-Hong Chen > Periodical Articles > Item 3990099045/15913

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/15913

Title:	Bloodmeals fuel dengue virus replication in the female mosquito Aedes aegypti
Authors:	Huang, YN;Lee, KY;Shiao, SH;Chen, CH;Yu, GY;Yu, MJ
Contributors:	National Mosquito-Borne Diseases Control Research Center;National Institute of Infectious Diseases and Vaccinology
Abstract:	Vector competence defines the ability of a vector to acquire, host, and transmit a pathogen. Understanding the molecular determinants of the mosquitos' competence to host dengue virus (DENV) holds promise to prevent its transmission. To this end, we employed RNA-seq to profile mRNA transcripts of the female Aedes aegypti mosquitos feeding on na & iuml;ve vs viremic mouse. While most transcripts (12,634) did not change their abundances, 360 transcripts showed decreases. Biological pathway analysis revealed representatives of the decreased transcripts involved in the wnt signaling pathway and hippo signaling pathway. One thousand three hundred fourteen transcripts showed increases in abundance and participate in 21 biological pathways including amino acid metabolism, carbon metabolism, fatty acid metabolism, and oxidative phosphorylation. Inhibition of oxidative phosphorylation with antimycin A reduced oxidative phosphorylation activity and ATP concentration associated with reduced DENV replication in the Aedes aegypti cells. Antimycin A did not affect the amounts of the non-structural proteins 3 and 5, two major components of the replication complex. Ribavirin, an agent that reduces GTP concentration, recapitulated the effects of reduced ATP concentration on DENV replication. Knocking down one of the oxidative phosphorylation components, ATP synthase subunit beta, reduced DENV replication in the mosquitos. In summary, our results suggest that DENV enhances metabolic pathways in the female Aedes aegypti mosquitos to supply nutrients and energy for virus replication. ATP synthase subunit beta knockdown might be exploited to reduce the mosquitos' competence to host and transmit DENV. IMPORTANCEThrough evolution, the mosquito-borne viruses have adapted to the blood-feeding behaviors of their opportunist hosts to fulfill a complete lifecycle in humans and mosquitos. Disruption in the mosquitos' ability to host these viruses offers strategies to prevent diseases caused by them. With the advent of genomic tools, we discovered that dengue virus (DENV) benefited from the female mosquitos' bloodmeals for metabolic and energetic supplies for replication. Chemical or genetic disruption in these supplies reduced DENV replication in the female mosquitos. Our discovery can be exploited to produce genetically modified mosquitos, in which DENV infection leads to disruption in the supplies and thereby reduces replication and transmission. Our discovery might be extrapolated to prevent mosquito-borne virus transmission and the diseases they cause.
Date:	2024-07
Relation:	Journal of Virology. 2024 Jul 23;98(7):Article number e0070124.
Link to:	http://dx.doi.org/10.1128/jvi.00701-24
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0022-538X&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:001251280500002
Cited Times(Scopus):	https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85199813541
Appears in Collections:	[Chun-Hong Chen] Periodical Articles [Guann-Yi Yu] Periodical Articles

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