Dengue virus infection modifies mosquito blood-feeding behavior to increase transmission to the host

Abstract

Mosquito blood-feeding behavior is a key determinant of the epidemiology of dengue viruses (DENV), the most-prevalent mosquito-borne viruses. However, despite its importance, how DENV infection influences mosquito blood-feeding and, consequently, transmission remains unclear. Here, we developed a high-resolution, video-based assay to observe the blood-feeding behavior of Aedes aegypti mosquitoes on mice. We then applied multivariate analysis on the high-throughput, unbiased data generated from the assay to ordinate behavioral parameters into complex behaviors. We showed that DENV infection increases mosquito attraction to the host and hinders its biting efficiency, the latter resulting in the infected mosquitoes biting more to reach similar blood repletion as uninfected mosquitoes. To examine how increased biting influences DENV transmission to the host, we established an in vivo transmission model with immuno-competent mice and demonstrated that successive short probes result in multiple transmissions. Finally, to determine how DENV-induced alterations of host-seeking and biting behaviors influence dengue epidemiology, we integrated the behavioral data within a mathematical model. We calculated that the number of infected hosts per infected mosquito, as determined by the reproduction rate, tripled when mosquito behavior was influenced by DENV infection. Taken together, this multidisciplinary study details how DENV infection modulates mosquito blood-feeding behavior to increase vector capacity, proportionally aggravating DENV epidemiology. By elucidating the contribution of mosquito behavioral alterations on DENV transmission to the host, these results will inform epidemiological modeling to tailor improved interventions against dengue.

Mosquito immune cells enhance dengue and Zika virus dissemination inAedes aegypti

“…While our study examines the influence of hemocytes in flavivirus (DENV and ZIKV) dissemination, the role of hemocytes in virus infection and dissemination may differ for other arboviruses. For instance, alphaviruses and flaviviruses have different strategies for replication and assembly [61][62][63] where alphaviruses typically replicate faster in the mosquito host. For example, chikungunya virus is able to quickly replicate and escape the midgut as early as 24 h after an infectious blood meal 15,64 , contrasting the approximate three days required for the earliest escape of ZIKV from the midgut 16 .…”

The significance of mosquito saliva in arbovirus transmission and pathogenesis in the vertebrate host

“…aegypti [105]. Furthermore, an infected mosquito shows increased probing and biting behaviour [155,156] or changed salivary gland physiology [157], which may eventually increase arbovirus transmission rates [97]. Using uninfected mosquito saliva or probing prior to virus inoculation in an in vivo model may therefore not recapitulate what happens in nature and yield differential results compared to infecting an animal model via an infectious mosquito bite.…”

Vector-Borne Viral Diseases as a Current Threat for Human and Animal Health—One Health Perspective

“…Nevertheless, it was documented that the introduction of the arbovirus to the vector body leads to transcriptomic and proteomic changes. Additionally, as it was proven in the example of DENV infecting the Aedes aegypti mosquito, arboviruses could also affect vector behavior by increasing the frequency of biting, which results in a higher probability of virus transmission [ 92 ]. Analysis of vectors collected from different geographic regions confirms that their genetic variation can often lead to differences in the activity of proteins that can determine their susceptibility and competence [ 93 , 94 ].…”