Dengue infection modulates locomotion and host seeking in Aedes aegypti

Abstract

Pathogens may manipulate their human and mosquito hosts to enhance disease transmission. Dengue, caused by four viral serotypes, is the fastest-growing transmissible disease globally resulting in 50-100 million infections annually. Transmission of the disease relies on the interaction between humans and the vector Aedes aegypti and is largely dependent on the odor-mediated host seeking of female mosquitoes. In this study, we use activity monitors to demonstrate that dengue virus-1 affects the locomotion and odor-mediated behavior of Ae. aegypti, reflecting the progression of infection within the mosquito. Mosquitoes 4-6 days post-infection increase locomotion, but do not alter their odor-driven host-seeking response. In contrast, females 14-16 days post-infection are less active, yet more sensitive to human odors as assessed by behavioral and electrophysiological assays. Such an increase in physiological and behavioral sensitivity is reflected by the antennal-specific increase in abundance of neural signaling transcripts in 14 days post-infection females, as determined by transcriptome analysis. This suggests that the sensitivity of the mosquito peripheral olfactory system is altered by the dengue virus by enhancing the overall neural responsiveness of the antenna, rather than the selective regulation of chemosensoryrelated genes. Our study reveals that dengue virus-1 enhances vector-related behaviors in the early stages post-infection that aid in avoiding predation and increasing spatial exploration. On the other hand, at the later stages of infection, the virus enhances the host-seeking capacity of the vector, thereby increasing the risk of virus transmission. A potential mechanism is discussed.

Modulation of odour-guided behaviour in mosquitoes

“…Pathogens obtained through an infected blood meal may affect the propensity of female mosquitoes to host seek and blood feed in subsequent gonotrophic cycles, in a pathogen-specific pattern (Anderson et al 1999 ; Grimstad et al 1980 ; Koella et al 1998 , 2002 ; Platt et al 1997 ; Tallon et al 2020 ; Vogels et al 2017 ; Wekesa et al 1992 ; Yan et al 2018 ). In addition, a study by Nyasembe et al ( 2014 ) demonstrated that female An.…”

“…aegypti , based on larval experience, was lost following dengue virus infection. These pathogen-induced changes in vector behaviour appear to be dependent on the progression of infection within the mosquito (Anderson et al 1999 ; Koella et al 2002 ; Tallon et al 2020 ), and are often regarded as an active manipulation by the pathogen to increase transmission. However, other studies imply that these changes merely occur as a result of a general immunological response (Cator et al 2013 ).…”

“…The modulation of olfactory behaviour in mosquitoes is underpinned by a highly plastic peripheral olfactory system (as described below), as opposed to that generally described in other insects (Gadenne et al 2016 ). Over the past 30 years we have been accumulating physiological evidence emphasising that OSNs of mosquitoes alter activity in response to intrinsic factors (Bohbot et al 2013 ; Davis 1984a , b ; Eilerts et al 2018 ; Grant and O’Connell 2007 ; Omondi et al 2015 ; Omondi et al 2019 ; Qiu et al 2006 ; Rund et al 2013b ; Siju et al 2010 ; Stanczyk et al 2019 ; Tallon et al 2020 ). With the advent of functional genomics, we are now starting to describe the molecular correlates that form the basis of the olfactory system regulation in mosquitoes.…”

“…In general, as female mosquitoes age, the incidence of plant feeding decreases and host seeking increases (Foster 1995 ; Gary and Foster 2006 ). Few studies have investigated the sensitivity of OSNs or the transcript abundance in the peripheral olfactory system of females in older host-seeking females, and these data are largely collected as controls for assessing state-dependent change (Davis 1984a ; Bohbot et al 2013 ; Hill et al accepted ; Tallon et al 2020 ), as there is low probability of finding older (> 10-day post-emergence) nulliparous females in the wild. Collectively, available data suggests that host seeking is regulated and modulated as the female ages, and this is, at least in part, due to changes in expression of the chemosensory-related genes in the peripheral olfactory system (Fig.…”

“…Pathogen-infected mosquitoes often exhibit altered odour-mediated behaviours (Koella et al 2002 ; Nyasembe et al 2014 ; Gaburro et al 2018a , b ; Tallon et al 2020 ), corresponding with post-infection changes in the sensitivity of the peripheral olfactory system to behaviourally relevant odorants (Stanczyk et al 2019 ; Tallon et al 2020 ) and neural activity patterns in the brain (Salazar et al 2007 ). Moreover, the abundance of many transcripts related to neural signalling change in response to pathogen infection in the antennae, heads, and bodies of mosquitoes (Emami et al 2017 ; Gaburro et al 2018a , b ; Salazar et al 2007 ; Tallon et al 2020 ), suggesting that neural signalling pathways may be one target of pathogen-induced modulation. In addition, a limited number of olfactory-related transcripts alter abundance in the antennae of host-seeking females capable of transmitting the pathogen (Tallon et al 2020 ), indicating that the regulation of these chemosensory transcripts is another target of pathogen manipulation.…”