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As mosquito-borne viruses, they can persistently infect the central nervous system of mosquitoes without causing symptoms, yet they can alter the physiology and behavior of these insects. However, the molecular mechanisms by which flaviviruses directly influence mosquito feeding behavior remain largely unexplored. Here, we show that dengue virus serotype 2 (DENV2) and Zika virus (ZIKV) elevate mosquito locomotor activity and blood-feeding propensity throughout the day. Untargeted metabolomics identified increased N-acetyl-L-tyrosine levels in virus-infected mosquito heads, which enhanced locomotor activity and blood-feeding efficiency when injected into\n                      <jats:italic toggle=\"yes\">Aedes aegypti<\/jats:italic>\n                      . Virus infection disrupted the circadian rhythm of\n                      <jats:italic toggle=\"yes\">tyrosine hydroxylase<\/jats:italic>\n                      (\n                      <jats:italic toggle=\"yes\">Aath<\/jats:italic>\n                      ), a key dopamine synthesis gene, maintaining its consistent elevation of expression throughout the day. Furthermore, DENV2 and ZIKV perturbed the molecular circadian core oscillator in\n                      <jats:italic toggle=\"yes\">Ae. aegypti<\/jats:italic>\n                      . Additionally, mosquitoes injected with L-3,4-dihydroxyphenylalanine exhibited higher locomotor activity and blood-sucking rates. In contrast, knockdown of\n                      <jats:italic toggle=\"yes\">Aath<\/jats:italic>\n                      reduced blood feeding and decreased infection rates in mice bitten by virus-infected mosquitoes. Collectively, our findings elucidate the molecular mechanisms by which DENV2 and ZIKV modulate the physiology and feeding behavior of\n                      <jats:italic toggle=\"yes\">Ae. aegypti<\/jats:italic>\n                      vectors, thereby facilitating the transmission of these viruses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>This study sheds light on how DENV2 and ZIKV affect the feeding behavior of mosquitoes. We discovered the molecular mechanisms that lead to increased movement and blood feeding in mosquitoes by altering neurotransmitter levels and disrupting their internal biological clocks. These findings reveal how these viruses enhance their own transmission by making mosquitoes more active. This research could help in developing strategies to target these processes, ultimately aiding efforts to control the spread of dengue and Zika viruses and reducing the risk of outbreaks.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.03968-24","type":"journal-article","created":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T09:01:27Z","timestamp":1745917287000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":7,"title":["DENV2 and ZIKV modulate the feeding behavior of\n                    <i>Aedes aegypti<\/i>\n                    by altering the tyrosine-dopamine pathway"],"prefix":"10.1128","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9530-8862","authenticated-orcid":true,"given":"Dongmin","family":"Gao","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02v51f717","id-type":"ROR","asserted-by":"publisher"}],"name":"New Cornerstone Science Laboratory, School 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