The SUMOylation pathway suppresses arbovirus replication in <i>Aedes aegypti</i> cells

Mosquitoes are responsible for the transmission of many clinically important arboviruses that cause significant levels of annual mortality and socioeconomic health burden worldwide. Deciphering the mechanisms by which mosquitoes modulate arbovirus infection is crucial to understand how viral-host interactions promote vector transmission and human disease. SUMOylation is a post-translational modification that leads to the covalent attachment of the Small Ubiquitin-like MOdifier (SUMO) protein to host factors, which in turn can modulate their stability, interaction networks, sub-cellular localisation, and biochemical function. While the SUMOylation pathway is known to play a key role in the regulation of host immune defences to virus infection in humans, the importance of this pathway during arbovirus infection in mosquito vectors, such as Aedes aegypti (Ae. aegypti), remains unknown. Here we characterise the sequence, structure, biochemical properties, and tissue-specific expression profiles of component proteins of the Ae. aegypti SUMOylation pathway. We demonstrate significant biochemical differences between Ae. aegypti and Homo sapiens SUMOylation pathways and identify cell-type specific patterns of SUMO expression in Ae. aegypti tissues known to support arbovirus replication. Importantly, depletion of core SUMOylation effector proteins (SUMO, Ubc9 and PIAS) in Ae. aegypti cells led to enhanced levels of arbovirus replication from three different families; Zika (Flaviviridae), Semliki Forest (Togaviridae), and Bunyamwera (Bunyaviridae) viruses. Our findings identify an important role for mosquito SUMOylation in the cellular restriction of arboviruses that may directly influence vector competence and transmission of clinically important arboviruses

Mosquito saliva enhances virus infection through sialokinin-dependent vascular leakage

Viruses transmitted by Aedes mosquitoes are an increasingly important global cause of disease. Defining common determinants of host susceptibility to this large group of het-erogenous pathogens is key for informing the rational design of panviral medicines. Infection of the vertebrate host with these viruses is enhanced by mosquito saliva, a complex mixture of salivary-gland-derived factors and microbiota. We show that the enhancement of infection by saliva was dependent on vascular function and was independent of most antisaliva immune responses, including salivary microbiota. Instead, the Aedes gene product sialokinin mediated the enhancement of virus infection through a rapid reduction in endothelial barrier integrity. Sialokinin is unique within the insect world as having a vertebrate-like tachykinin sequence and is absent from Anopheles mosquitoes, which are incompetent for most arthropod-borne viruses, whose saliva was not proviral and did not induce similar vascular permeability. Therapeutic strategies targeting sialokinin have the potential to limit disease severity following infection with Aedes mosquito-borne viruses.</p

Advancing vector biology research: a community survey for future directions, research applications and infrastructure requirements

Vector-borne pathogens impact public health, animal production, and animal welfare. Research on arthropod vectors such as mosquitoes, ticks, sandflies, and midges which transmit pathogens to humans and economically important animals is crucial for development of new control measures that target transmission by the vector. While insecticides are an important part of this arsenal, appearance of resistance mechanisms is increasingly common. Novel tools for genetic manipulation of vectors, use of Wolbachia endosymbiotic bacteria, and other biological control mechanisms to prevent pathogen transmission have led to promising new intervention strategies, adding to strong interest in vector biology and genetics as well as vector-pathogen interactions. Vector research is therefore at a crucial juncture, and strategic decisions on future research directions and research infrastructure investment should be informed by the research community. A survey initiated by the European Horizon 2020 INFRAVEC-2 consortium set out to canvass priorities in the vector biology research community and to determine key activities that are needed for researchers to efficiently study vectors, vector-pathogen interactions, as well as access the structures and services that allow such activities to be carried out. We summarize the most important findings of the survey which in particular reflect the priorities of researchers in European countries, and which will be of use to stakeholders that include researchers, government, and research organizations

The Aedes aegypti Domino ortholog, p400 regulates antiviral exogenous siRNA pathway activity through control of ago-2 levels

This dataset contains the source data that will make up the figures for the pape

Evolution of sexually-transferred steroids and mating-induced phenotypes in Anopheles mosquitoes

Human malaria, which remains a major public health problem, is transmitted by a subset of Anopheles mosquitoes belonging to only three out of eight subgenera: Anopheles, Cellia and Nyssorhynchus. Unlike almost every other insect species, males of some Anopheles species produce steroid hormones which are transferred to females during copulation to influence their reproduction. Steroids are consequently a potential target for malaria vector control. Here, we analysed the evolution of sexually-transferred steroids and their effects on female reproductive traits across Anopheles by using a set of 16 mosquito species (five Anopheles, eight Cellia, and three Nyssorhynchus), including malaria vector and non-vector species. We show that male steroid production and transfer are specific to the Cellia and therefore represent a synapomorphy of this subgenus. Furthermore, we show that mating-induced effects in females are variable across species and differences are not correlated with sexually-transferred steroids or with Anopheles ability to transmit human malaria. Overall, our findings highlight that Anopheles mosquitoes have evolved different reproductive strategies, independently of being a malaria vector or not

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In Fraktu

Anopheles gambiae males produce and transfer the vitellogenic steroid hormone 20-hydroxyecdysone to females during mating

In female insects, the steroid hormone 20-hydroxyecdysone (20E) plays a major role in activating vitellogenesis, a process required for egg development. By contrast with vertebrates, production of large amounts of hormonal steroids has not been reported in adult male insects. In the present study, we analyzed steroidogenesis in both male and female adult of the malaria mosquito Anopheles gambiae and we found that A. gambiae male mosquitoes produce high amounts of the steroid hormone 20E. Importantly, we found that male accessory glands, but not testes, are the source of 20E. Moreover, this steroid hormone is stored in male accessory glands and delivered to females during mating. These findings suggest that male 20E may not act as a true male sex steroid, but more likely as an allohormone. Our results give new insights into species-specific physiological processes that govern the reproductive success of the malaria mosquito. This could thus lead to the identification of new target genes for manipulating male and/or female reproductive success, a promising way to reduce or eliminate mosquito population and therefore to control malaria transmission

Standmengenverbesserung von Schmiedegesenken Vortraege von Forschungsinstituten

TIB: RO 8931(16) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Evolution of sexually-transferred steroids and mating-induced phenotypes in Anopheles mosquitoes

Abstract Human malaria, which remains a major public health problem, is transmitted by a subset of Anopheles mosquitoes belonging to only three out of eight subgenera: Anopheles, Cellia and Nyssorhynchus. Unlike almost every other insect species, males of some Anopheles species produce steroid hormones which are transferred to females during copulation to influence their reproduction. Steroids are consequently a potential target for malaria vector control. Here, we analysed the evolution of sexually-transferred steroids and their effects on female reproductive traits across Anopheles by using a set of 16 mosquito species (five Anopheles, eight Cellia, and three Nyssorhynchus), including malaria vector and non-vector species. We show that male steroid production and transfer are specific to the Cellia and therefore represent a synapomorphy of this subgenus. Furthermore, we show that mating-induced effects in females are variable across species and differences are not correlated with sexually-transferred steroids or with Anopheles ability to transmit human malaria. Overall, our findings highlight that Anopheles mosquitoes have evolved different reproductive strategies, independently of being a malaria vector or not