Immune Response and Development in Insects

The exceptional impact of the COVID-19 pandemic has stimulated an intense search for antiviral molecules. Host-targeted antiviral molecules have the potential of presenting broad-spectrum antiviral activity and are also considered as less likely to select for resistant viruses. In this study, we investigated the antiviral activity exerted by AM-001, a specific pharmacological inhibitor of EPAC1, a host exchange protein directly activated by cyclic AMP (cAMP). The cAMP-sensitive protein, EPAC1 regulates various physiological and pathological processes but its role in SARS-CoV-2 and influenza A virus infection has not yet been studied. Here, we provide evidence that the EPAC1 specific inhibitor AM-001 exerts potent antiviral activity against SARS-CoV-2 in the human lung Calu-3 cell line and the African green monkey Vero cell line. We observed a concentration-dependent inhibition of SARS-CoV-2 infectious viral particles and viral RNA release in the supernatants of AM-001 treated cells that was not associated with a significant impact on cellular viability. Furthermore, we identified AM-001 as an inhibitor of influenza A virus in Calu-3 cells. Altogether these results identify EPAC1 inhibition as a promising therapeutic target against viral infections.

France has been rabies-free among nonflying mammals since 2001. Despite this status, the rabies virus has been introduced several times through noncommercial pet movements, posing a threat of infection by this 100%-lethal zoonosis among local animal and human populations. To quantify the risk of rabies being introduced through worldwide noncommercial dog and cat movements, we performed a quantitative risk assessment using stochastic scenario tree modeling. The mean annual probability of at least one rabies introduction incident was 0.35 (median: 0.24, 90% prediction interval (PI) [0.04; 0.98]) and the mean annual number of rabies-infected pets introduced through pet movements was 0.96 (median: 0.27, 90% PI [0.04; 3.88]). These results highlight a nonnegligible, even high risk due to the associated consequences of such events. In alternative scenario testing, preventive anti-rabies vaccination proved to be an effective measure since removing the vaccination requirement led to a>15-fold increase in risk. The serological testing requirement had less of an effect (approximately two-fold increase when removed) and the posttest waiting period to ensure that antibodies were not linked to an infection had a negligible effect. Any change in pet owner compliance, especially regarding vaccination, could have a major impact on the risk. This study also shows that reinforced border control staff training could be more effective in reducing risk than more frequent checks. These results provide quantitative data for assessing the probability of the rabies virus entering France, and could help policymakers decrease this risk in rabies-free areas.

In Europe, Puumala virus (PUUV) transmitted by the bank vole (Myodes glareolus) is the causative agent of nephropathia epidemica (NE), a mild form of haemorrhagic fever with renal syndrome. In France, very little is known about the spatial and temporal variability of the virus circulating within bank vole populations. The present study involved monitoring of bank vole population dynamics and PUUV microdiversity over a ten-year period (2000–2009) in two forests of the Ardennes region: Elan and Croix-Scaille. Ardennes region is characterised by different environmental conditions associated with different NE epidemiology. Bank vole density and population parameters were estimated using the capture/marking/recapture method, and blood samples were collected to monitor the overall seroprevalence of PUUV in rodent populations. Phylogenetic analyses of fifty-five sequences were performed to illustrate the genetic diversity of PUUV variants between forests. The pattern of the two forests differed clearly. In the Elan forest, the rodent survival was higher, and this limited turn-over resulted in a lower seroprevalence and diversity of PUUV sequences than in the Croix-Scaille forest. Uncovering the links between host dynamics and virus microevolution is improving our understanding of PUUV distribution in rodents and the NE risk.

La perte de biodiversité est aujourd’hui confirmée, même si certains débats montrent la difficulté de tirer de ce constat les conséquences qui peuvent en résulter pour l’action humaine. Les sciences de la biodiversité se concentrent aujourd’hui fortement sur les mécanismes au travers desquels l’adaptation aux changements globaux se produit, et peut être accompagnée, et sur la définition de scénarios d’évolution plausibles redéfinissant les relations entre les sociétés et les écosystèmes.

The toxicity of 2 reduced-risk pesticides, 2% horticultural oil with 0.05% Silwet L-77 and Grandevo (Chromobacterium subtsugae Strain PRAA4-1T), to 2 predators: Metaseiulus occidentalis (Nesbitt) (Acari: Phytoseiidae) and Hemicheyletia wellsina DeLeon (Acari: Cheyletidae), and 3 orchid pests: the two-spotted spider mite Tetranychus urticae Koch (Prostigmata: Tetranychidae), the phalaenopsis mite, Tenuipalpus pacificus Baker (Acari: Tenuipalpidae), and the longtailed mealybug Pseudococcus longispinus (Targioni-Tozzetti) (Hemiptera: Pseudococcidae) were tested. Grandevo did not kill either predator, and it failed to suppress populations of T. urticae and P. longispinus, but it reduced T. pacificus by 84%. The Silwet and horticultural oil mixture caused mortality of at least 82% in all 5 species tested.

Porphytin-oligonudeotide hybrids containing one to four DNA strands (P1-P4) have been synthesised and fully characterised. The hybrid P4, which inserts one porphyrin and four DNA fragments, was combined with gold nanoparticles and images by electron microscopy.

A field test of integrated vector control was conducted in a tropical urban setting with a combination of a floating, slow-release, granular formulation of Bacillus sphaericus and environmental engineering measures (renovation of roads, collective water pumps, and cesspool lids). The targets were Culex quinquefasciatus and Anopheles gambiae in the two biggest towns of Burkina Faso (West Africa). Within the intervention zone, water pumping stations were improved and the surroundings drained to prevent the accumulation of stagnant water. Roads were leveled and given either simple gutters on each side or a concrete channel on one side to drain runoff water. Garbage containers were installed to provide an alternative to the drainage channels for waste disposal. Septic tanks were modified so that they could be emptied without destroying their lid. This study showed that it is possible to implement mosquito control in a tropical urban environment with teams of young people rapidly trained to apply a biological larvicide without any tools other than an iron bar to lift cesspool lids. Environmental improvements were initially costly, but demanded little subsequent expenditure. Local inhabitants' committees were mobilized to provide people with information and monitor the efficacy of the measures. Compared with what people spent individually on mosquito prevention and malaria medicine, these measures were not expensive, but many expected the community to pay for them from existing taxes, e.g., for water treatment and disposal. The necessary funding and logistics require a municipal organization with neighborhood support, if the measures are to be effective.

The homeostasis of the immune response requires tight regulation of the proliferation and apoptosis of activated lymphocytes. In humans, defects in immune homeostasis result in lymphoproliferation disorders including autoimmunity, haemophagocytic lymphohystiocytosis and lymphomas. The X-linked lymphoproliferative syndrome (XLP) is a rare, inherited immunodeficiency that is characterized by lymphohystiocytosis, hypogammaglobulinaemia and lymphomas, and that usually develops in response to infection with Epstein-Barr virus (EBV). Mutations in the signalling lymphocyte activation molecule (SLAM)-associated protein SAP, a signalling adaptor molecule, underlie 60% of cases of familial XLP. Here, we identify mutations in the gene that encodes the X-linked inhibitor-of-apoptosis XIAP (also termed BIRC4) in patients with XLP from three families without mutations in SAP. These mutations lead to defective expression of XIAP. We show that apoptosis of lymphocytes from XIAP-deficient patients is enhanced in response to various stimuli including the T-cell antigen receptor (TCR)-CD3 complex, the death receptor CD95 (also termed Fas or Apo-1) and the TNF-associated apoptosis-inducing ligand receptor (TRAIL-R). We also found that XIAP-deficient patients, like SAP-deficient patients, have low numbers of natural killer T-lymphocytes (NKT cells), indicating that XIAP is required for the survival and/or differentiation of NKT cells. The observation that XIAP-deficiency and SAP-deficiency are both associated with a defect in NKT cells strengthens the hypothesis that NKT cells have a key role in the immune response to EBV. Furthermore, by identifying an XLP immunodeficiency that is caused by mutations in XIAP, we show that XIAP is a potent regulator of lymphocyte homeostasis in vivo.