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Rift Valley fever (RVF) is a zoonotic arboviral disease that causes recurrent epidemics in Africa that may trigger fatal neurological disorders. However, the mechanisms of neuroinvasion by which the RVF virus (RVFV) reaches the human central nervous system (CNS) remain poorly characterized. In particular, it is not clear how RVFV is able to cross the human blood-brain barrier (hBBB), which is a neurovascular endothelium that protects the brain by regulating brain and blood exchanges. To explore these mechanisms, we used an in vitro hBBB model to mimic in vivo hBBB selectiveness and apicobasal polarity. Our results highlight the ability of RVFV to cross the hBBB by direct infection in a non-structural protein S (NSs)-independent but strain-dependent manner, leading to astrocyte and pericyte infections. Interestingly, RVFV infection did not induce hBBB disruption and was associated with progressive elimination of infected cells with no impairment of the tight junction protein scaffold and barrier function. Our work also shows that NSs, a well described RVFV virulence factor, limited the establishment of the hBBB-induced innate immune response and subsequent lymphocyte recruitment. These results provide in vitro confirmation of the ability of RVFV to reach human CNS by direct infection of the hBBB without altering its barrier function, and provide new directions to explore human RVFV neurovirulence and neuroinvasion mechanisms.IMPORTANCEThe RVF virus (RVFV) is capable of infecting humans and inducing severe and fatal neurological disorders. Neuropathogenesis and human central nervous system (CNS) invasion mechanisms of RVFV are still unknown, with only historical studies of autopsy data from fatal human cases in the 1980s and exploration studies in rodent models. One of the gaps in understanding RVFV human pathogenesis is how RVFV is able to cross the blood-brain barrier (BBB) in order to reach the human CNS. For the first time, we show that RVFV is able to directly infect cells of the human BBB in vitro to release viral particles into the human CNS, a well-characterized neuroinvasion mechanism of pathogens. Furthermore, we demonstrate strain-dependent variability of this neuroinvasion mechanism, identifying possible viral properties that could be explored to prevent neurological disorders during RVFV outbreaks., Competing Interests: The authors declare no conflict of interest.

Usutu virus (USUV) and West Nile virus (WNV) are two closely related emerging mosquito-borne flaviviruses. Their natural hosts are wild birds, but they can also cause severe neurological disorders in humans. Both viruses are efficiently suppressed by type I interferon (IFN), which interferes with viral replication, dissemination, pathogenesis and transmission. Here, we show that the replication of USUV and WNV are inhibited through a common set of IFN-induced genes (ISGs), with the notable exception of ISG20, which USUV is resistant to. Strikingly, USUV was the only virus among all the other tested mosquito-borne flaviviruses that demonstrated resistance to the 3'-5' exonuclease activity of ISG20. Our findings highlight that the intrinsic resistance of the USUV genome, irrespective of the presence of cellular or viral proteins or protective post-transcriptional modifications, relies on a unique sequence present in its 3' untranslated region. Importantly, this genomic region alone can confer ISG20 resistance to a susceptible flavivirus, without compromising its infectivity, suggesting that it could be acquired by other flaviviruses. This study provides new insights into the strategy employed by emerging flaviviruses to overcome host defense mechanisms., (© 2024. The Author(s).)

Flaviviruses comprise a large number of arthropod-borne viruses, some of which are associated with life-threatening diseases. Flavivirus infections are rising worldwide, mainly due to the proliferation and geographical expansion of their vectors. The main human pathogens are mosquito-borne flaviviruses, including dengue virus, Zika virus, and West Nile virus, but tick-borne flaviviruses are also emerging. As with any viral infection, the body's first line of defense against flavivirus infections is the innate immune defense, of which type I interferon is the armed wing. This cytokine exerts its antiviral activity by triggering the synthesis of hundreds of interferon-induced genes (ISGs), whose products can prevent infection. Among the ISGs that inhibit flavivirus replication, certain tripartite motif (TRIM) proteins have been identified. Although involved in other biological processes, TRIMs constitute a large family of antiviral proteins active on a wide range of viruses. Furthermore, whereas some TRIM proteins directly block viral replication, others are positive regulators of the IFN response. Therefore, viruses have developed strategies to evade or counteract TRIM proteins, and some even hijack certain TRIM proteins to their advantage. In this review, we summarize the current state of knowledge on the interactions between flaviviruses and TRIM proteins, covering both direct and indirect antiviral mechanisms.

Anticancer immunotherapies are therapeutics aimed at eliciting immune responses against tumor cells. Immunotherapies based on adoptive transfer of engineered immune cells have raised great hopes of cures because of the success of chimeric antigen receptor T-cell therapy in treating some hematologic malignancies. In parallel, advances in detailed analyses of the microenvironment of many solid tumors using high-dimensional approaches have established the origins and abundant presence of tumor-associated macrophages. These macrophages have an anti-inflammatory phenotype and promote tumor growth through a variety of mechanisms. Attempts have been made to engineer macrophages with chimeric receptors or transgenes to counteract their protumor activities and promote their antitumor functions such as phagocytosis of cancer cells, presentation of tumor antigens, and production of inflammatory cytokines. In this review, we cover current breakthroughs in engineering myeloid cells to combat cancer as well as potential prospects for myeloid-cell treatments., (©2022 American Association for Cancer Research.)

Forest management can benefit from decision support tools, including GIS-based multicriteria decision-aiding approach. In the Mediterranean region, Pinus pinaster forests play a very important role in biodiversity conservation and offer many socioeconomic benefits. However, the conservation of this species is affected by the increase in forest fires and the expansion of Matsucoccus feytaudi. This paper proposes a methodology based on commonly available data for assessing the values and risks of P. pinaster forests and to generating maps to aid in decisions pertaining to fire and phytosanitary risk management. The criteria for assessing the values (land cover type, legislative tools for biodiversity conservation, environmental tourist sites and access routes, and timber yield) and the risks (fire and phytosanitation) of P. pinaster forests were obtained directly or by considering specific indicators, and they were subsequently aggregated by means of GIS-based multicriteria analysis. This approach was tested on the island of Corsica (France), and maps to aid in decisions pertaining to fire risk and phytosanitary risk (M. feytaudi) were obtained for P. pinaster forest management. Study results are used by the technical offices of the local administration-Corsican Agricultural and Rural Development Agency (ODARC)-for planning the conservation of P. pinaster forests with regard to fire prevention and safety and phytosanitary risks. The decision maker took part in the evaluation criteria study (weight, normalization, and classification of the values). Most suitable locations are given to target the public intervention. The methodology presented in this paper could be applied to other species and in other Mediterranean regions.

Polyphenol compounds were extracted from Myrtus communis L. berries (Myrtaceae) by maceration in 70% ethanol and analysed by HPLC-DAD and electrospray mass spectrometry. The Myrtus berries were collected at maturity from seven localities on the island of Corsica (France) and the sampling was carried out during three years. The polyphenol composition of Corsican Myrtus berries was characterized by two phenolic acids, four flavanols, three flavonols and five flavonol glycosides. The major compounds were myricetin-3-O-arabinoside and myricetin-3-O-galactoside. Principal components analysis (PCA) is applied to study the chemical composition and variability of myrtle berries alcoholic extracts from the seven localities. Canonical analysis and PCA data distinguishes two groups of myrtle berries characterized by different concentrations of polyphenols according to soil and years of harvest. The variations in the polyphenol concentration were due to biotic and abiotic factors.

Fire is a dominant ecological factor in Mediterranean-type ecosystems. Forest management includes many preventive tools, in particular for fire prevention, such as mechanical treatments and prescribed burning. Prescribed burning is a commonly used method for treating fuel loads, but fuel reduction targets for reducing wildfire hazards must be balanced against fuel retention targets in order to maintain habitat and other forest functions. This approach was used on Pinus nigra ssp laricio var. Corsicana, a pine endemic to Corsica of great ecological and economic importance. Many studies of plant phenolic compounds have been carried out concerning responses to various stresses. The aim of this study was to understand i) the effects of prescribed burning 1 to 16 months later and ii) the effects of the seasonality of burning, spring or fall, on the production of phenolic compounds in Pinus laricio. After prescribed burning conducted in spring, Pinus laricio increases the synthesis of total phenolic compounds for a period of 7 months. The increase is greater after spring-burning than fall-burning. With regard to simple phenols, only dihydroferulic acid responds about 1 year after both types of prescribed burning. The causes of these increases are discussed in this paper. Total phenolic compounds could be used as a bioindicator for the short-term response of Pinus laricio needles to prescribed burning. Simple phenols may be useful for revealing the medium-term effects of prescribed burning. The results of this study include recommending forest managers to use prescribed burning in the fall rather than spring to reduce fuel loads and have less impact on the trees.

Fire is a dominant ecological factor in Mediterranean-type ecosystems. Management strategies include prescribed (controlled) burning, which has been used in the management of several species, such as Pinus nigra ssp laricio var. Corsicana, a pine endemic to Corsica of great ecological and economic importance. The effects of prescribed burning on Pinus laricio have been little studied. The first aim of this study was to characterize total and simple phenolic compounds in Pinus laricio. The second aim was to understand: i) the short term (one to three months) and medium term (three years) effects of prescribed burning, and ii) the effects of periodic prescribed burning on the production of phenolic compounds in Pinus laricio. The first result of this study is the presence of total and simple phenolic compounds in the needles of Pinus laricio. 3-Vanillyl propanol is the major compound. After a prescribed burning, the synthesis of total phenolic compounds increases in Pinus laricio for a period of three months. Total phenolic compounds could be used as bioindicators for the short-term response of Pinus laricio needles to prescribed burning. Simple phenolic compounds do not seem to be good indicators of the impact of prescribed burning because prescribed burnings are low in intensity.

In recent times, more and more studies have focused on flavonoids as biomarkers of environmental quality in aquatic plants, in particular, Posidonia oceanica (Linnaeus) Delile. It is therefore of interest to determine how different prehandling methods can affect flavonoid concentrations. The methods tested were (1) immediate extraction of fresh samples, (2) extraction after 48 hr chilling, (3) freeze-drying, and (4) oven drying. Chilling and freeze-drying considerably altered the quantity of flavonoids measured, but not their profile. The effect of oven drying was not significant. Chilling led to a loss of 57% of total (pro)anthocyanidins, 39% of total flavonols, and 48% of all simple flavonols (myricetin, quercetin, isorhamnetin, and kaempferol). Freeze-drying caused a loss of 71% of total (pro)anthocyanidins, 87% of total flavonols, and 95% of all simple flavonols.

This work is a first approach to flavonoid responses (total proanthocyanidins and total and simple flavonols) in Posidonia oceanica in function of nutrient enrichment (aquaculture activities - fish farming), in the western Mediterranean Sea (Calvi-Corsica-France). The first result is the presence of total and simple flavonoids in P. oceanica. The second result shows an increase in total proanthocyanidin and total flavonol concentrations near cages, which would be linked to the high grazing pressure induced by meadow enrichment. Concerning simple flavonols, only quercetin shows a response to fish farming, which could be due to its strong antioxidant capacity. The presence of fish farming, which causes variations in environmental parameters, could affect the functioning of P. oceanica meadows. Flavonoid concentrations in P. oceanica seem to be a possible bioindicator of nutrient enrichment for the management of the littoral environment.