Programme in Emerging Infectious Diseases, Duke-National University of Singapore (NUS) Medical School, Singapore 169857, Singapore.
Department of Biological Sciences, National University of Singapore, Singapore 117558, Singapore.
Proc Natl Acad Sci U S A. 2022 Jan 18;119(3). doi: 10.1073/pnas.2117589119.
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 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.
蚊子的吸血行为是登革热病毒（DENV）流行病学的关键决定因素，DENV 是最普遍的蚊媒病毒。然而，尽管其重要性不言而喻，但 DENV 感染如何影响蚊子的吸血行为，以及由此导致的传播仍不清楚。在这里，我们开发了一种基于高分辨率视频的 assay，以观察蚊子在老鼠身上的吸血行为。然后，我们对 assay 生成的高通量、无偏数据进行多元分析，将行为参数有序排列成复杂的行为。我们表明，DENV 感染增加了蚊子对宿主的吸引力，并阻碍了其吸血效率，后者导致感染的蚊子叮咬更多以达到与未感染蚊子相似的血液充盈度。为了研究增加的叮咬如何影响 DENV 向宿主的传播，我们用免疫功能正常的老鼠建立了一个体内传播模型，并证明连续的短探针会导致多次传播。最后，为了确定 DENV 诱导的宿主寻找和叮咬行为改变如何影响登革热流行病学，我们将行为数据整合到一个数学模型中。我们计算得出，当蚊子的行为受到 DENV 感染的影响时，由繁殖率决定的每只感染蚊子感染的宿主数量增加了两倍。总之，这项多学科研究详细说明了 DENV 感染如何调节蚊子的吸血行为以增加媒介容量，从而使 DENV 流行病学呈比例加重。通过阐明蚊子行为改变对 DENV 向宿主传播的贡献，这些结果将为针对登革热的流行病学模型提供信息，以制定改进的干预措施。
