Emergence of SARS-CoV-2 causing COVID-19 has resulted in hundreds of thousands of deaths. In search for key targets of effective therapeutics, robust animal models mimicking COVID-19 in humans are urgently needed. Here, we show that Syrian hamsters, in contrast to mice, are highly permissive to SARS-CoV-2 and develop bronchopneumonia and strong inflammatory responses in the lungs with neutrophil infiltration and edema, further confirmed as consolidations visualized by micro-CT alike in clinical practice. Moreover, we identify an exuberant innate immune response as key player in pathogenesis, in which STAT2 signaling plays a dual role, driving severe lung injury on the one hand, yet restricting systemic virus dissemination on the other. Our results reveal the importance of STAT2-dependent interferon responses in the pathogenesis and virus control during SARS-CoV-2 infection and may help rationalizing new strategies for the treatment of COVID-19 patients.

Introductory paragraphSince the emergence of SARS-CoV-2 causing COVID-19, the world is being shaken to its core with numerous hospitalizations and hundreds of thousands of deaths. In search for key targets of effective therapeutics, robust animal models mimicking COVID-19 in humans are urgently needed. Here, we show that productive SARS-CoV-2 infection in the lungs of mice is limited and restricted by early type I interferon responses. In contrast, we show that Syrian hamsters are highly permissive to SARS- CoV-2 and develop bronchopneumonia and a strong inflammatory response in the lungs with neutrophil infiltration and edema. Moreover, we identify an exuberant innate immune response as a key player in pathogenesis, in which STAT2 signaling plays a dual role, driving severe lung injury on the one hand, yet restricting systemic virus dissemination on the other. Finally, we assess SARS-CoV- 2-induced lung pathology in hamsters by micro-CT alike used in clinical practice. Our results reveal the importance of STAT2-dependent interferon responses in the pathogenesis and virus control during SARS-CoV-2 infection and may help rationalizing new strategies for the treatment of COVID-19 patients.

Insecticide resistance is a worldwide threat for vector control around the world, and Aedes aegypti, the main vector of several arboviruses, is a particular concern. To better understand the mechanisms of resistance, four isofemale strains originally from French Guiana were isolated and analysed using combined approaches. The activity of detoxification enzymes involved in insecticide resistance was assayed, and mutations located at positions 1016 and 1534 of the sodium voltage-gated channel gene, which have been associated with pyrethroid resistance in Aedes aegypti populations in Latin America, were monitored. Resistance to other insecticide families (organophosphates and carbamates) was evaluated. A large-scale proteomic analysis was performed to identify proteins involved in insecticide resistance. Our results revealed a metabolic resistance and resistance associated with a mutation of the sodium voltage-gated channel gene at position 1016. Metabolic resistance was mediated through an increase of esterase activity in most strains but also through the shifts in the abundance of several cytochrome P450 (CYP450s). Overall, resistance to deltamethrin was linked in the isofemale strains to resistance to other class of insecticides, suggesting that cross- and multiple resistance occur through selection of mechanisms of metabolic resistance. These results give some insights into resistance to deltamethrin and into multiple resistance phenomena in populations of Ae. aegypti.

Since the 1940s, French Guiana has implemented vector control to contain or eliminate malaria, yellow fever, and, recently, dengue, chikungunya, and Zika. Over time, strategies have evolved depending on the location, efficacy of the methods, development of insecticide resistance, and advances in vector control techniques. This review summarises the history of vector control in French Guiana by reporting the records found in the private archives of the Institute Pasteur in French Guiana and those accessible in libraries worldwide. This publication highlights successes and failures in vector control and identifies the constraints and expectations for vector control in this French overseas territory in the Americas.

Culex modestus mosquitoes are considered to be a potential “bridge” vector, being able to transmit pathogens between birds as well as from birds to mammals, including humans. In Belgium, this mosquito species was considered absent until the finding of one larva in 2018 and subsequent evidence of a large population in 2019 to 2020 described here.

In this study, we first utilized the single mosquito microbiome analysis, demonstrating a complex three-way interaction among arboviruses, resident microbiota, and the host, which is distinct for different arbovirus–mosquito combinations. Some of the previously described “core virus” increased in the mosquitos receiving viral blood meal, like Guadeloupe mosquito virus and Guadeloupe Culex tymo-like virus, suggesting their potential roles in ZIKV and WNV infection.

Arthropod-borne viruses contribute significantly to global mortality and morbidity in humans and animals. These viruses are mainly transmitted between susceptible vertebrate hosts by hematophagous arthropod vectors, especially mosquitoes. Recently, there has been substantial attention for a novel group of viruses, referred to as insect-specific viruses (ISVs) which are exclusively maintained in mosquito populations. Recent discoveries of novel insect-specific viruses over the past years generated a great interest not only in their potential use as vaccine and diagnostic platforms but also as novel biological control agents due to their ability to modulate arbovirus transmission. While arboviruses infect both vertebrate and invertebrate hosts, the replication of insect-specific viruses is restricted in vertebrates at multiple stages of virus replication. The vertebrate restriction factors include the genetic elements of ISVs (structural and non-structural genes and the untranslated terminal regions), vertebrate host factors (agonists and antagonists), and the temperature-dependent microenvironment. A better understanding of these bottlenecks is thus warranted. In this review, we explore these factors and the complex interplay between ISVs and their hosts contributing to this host restriction phenomenon.

Culex modestus is a mosquito species with a relevant role in the transmission of West Nile virus and Usutu virus. Its presence has been reported across Europe, yet it is absent in Belgium. Field mosquitoes in the city of Leuven and surroundings were collected in the summer of 2019 and 2020. Species identification was performed by morphological features and partial sequences of the mitochondrial cytochrome oxidase subunit 1 (COI) gene. In order to examine the genetic structure of the Cx. modestus population found in Leuven, mitochondrial sequences of Cx. modestus mosquitoes collected in other 8 countries across Europe were retrieved from GenBank and confronted to the COI sequences from Belgian mosquitoes to construct a haplotype network.Hereby, we confirmed the new establishment of Cx. modestus in the surroundings of Leuven, Belgium. Haplotype network analysis showed that the Belgian population is rather diverse, suggesting that it must have been establish in Belgium for some time. The Belgian population was most closely related to Cx. modestus populations from the UK and Germany. The NetoVIR protocol was used to study the virome of 8 pools of mosquitoes. At least 33 eukaryotic viral species were identified. Nine (near-)complete genomes belonging to 6 viral species were identified, named Culex totivirus Leu1, Leu2 and Leu3, Alphamesonivirus Leu4, Iflavirus Leu5 and Leu6, Negevirus Leu7 and Leu8, and Rhabdovirus Leu9, all of which were closely related to known viruses. In conclusion, with the introduction of Cx. modestus in Belgium, the evaluation of its potential role in the transmission of arboviruses that could cause disease in animals and humans is necessary.Importance for non-specialistCulex modestus is a mosquito species that plays a role in nature as a ‘bridge’ vector, being able to transmit pathogens between birds, as well as from birds to mammals, including humans. In Belgium, this species was considered absent. Field mosquitoes were collected in urban, peri-urban and wetland areas in the summer of 2019 and 2020 in Leuven, and morphological and molecular methods were performed to confirm the presence of Cx. modestus in this region. The ability of mosquitoes to transmit pathogens can depend on a lot of factors, one of them being the natural virus composition in their bodies. For this purpose, we aimed to identify the whole virus group harbored by Belgian mosquitoes. This could provide more insight for mosquito and, therefore, disease control. Besides, the introduction of Cx. modestus may increase the risk of disease transmission. It is advisable to implement mosquito surveillance programs monitoring this species.