MHC class II proteins mediate sialic acid independent entry of human and avian H2N2 influenza A viruses.

Influenza A viruses (IAV) pose substantial burden on human and animal health. Avian, swine and human IAV bind sialic acid on host glycans as receptor, whereas some bat IAV require MHC class II complexes for cell entry. It is unknown how this difference evolved and whether dual receptor specificity is possible. Here we show that human H2N2 IAV and related avian H2N2 possess dual receptor specificity in cell lines and primary human airway cultures. Using sialylation-deficient cells, we reveal that entry via MHC class II is independent of sialic acid. We find that MHC class II from humans, pigs, ducks, swans and chickens but not bats can mediate H2 IAV entry and that this is conserved in Eurasian avian H2. Our results demonstrate that IAV can possess dual receptor specificity for sialic acid and MHC class II, and suggest a role for MHC class II-dependent entry in zoonotic IAV infections.

Stability of influenza A virus in droplets and aerosols is heightened by the presence of commensal respiratory bacteria.

Aerosol transmission remains a major challenge for control of respiratory viruses, particularly those causing recurrent epidemics, like influenza A virus (IAV). These viruses are rarely expelled alone, but instead are embedded in a consortium of microorganisms that populate the respiratory tract. The impact of microbial communities and inter-pathogen interactions upon stability of transmitted viruses is well-characterized for enteric pathogens, but is under-studied in the respiratory niche. Here, we assessed whether the presence of five different species of commensal respiratory bacteria could influence the persistence of IAV within phosphate-buffered saline and artificial saliva droplets deposited on surfaces at typical indoor air humidity, and within airborne aerosol particles. In droplets, presence of individual species or a mixed bacterial community resulted in 10- to 100-fold more infectious IAV remaining after 1 h, due to bacterial-mediated flattening of drying droplets and early efflorescence. Even when no efflorescence occurred at high humidity or the bacteria-induced changes in droplet morphology were abolished by aerosolization instead of deposition on a well plate, the bacteria remained protective. Staphylococcus aureus and Streptococcus pneumoniae were the most stabilizing compared to other commensals at equivalent density, indicating the composition of an individual's respiratory microbiota is a previously unconsidered factor influencing expelled virus persistence.IMPORTANCEIt is known that respiratory infections such as coronavirus disease 2019 and influenza are transmitted by release of virus-containing aerosols and larger droplets by an infected host. The survival time of viruses expelled into the environment can vary depending on temperature, room air humidity, UV exposure, air composition, and suspending fluid. However, few studies consider the fact that respiratory viruses are not alone in the respiratory tract-we are constantly colonized by a plethora of bacteria in our noses, mouth, and lower respiratory system. In the gut, enteric viruses are known to be stabilized against inactivation and environmental decay by gut bacteria. Despite the presence of a similarly complex bacterial microbiota in the respiratory tract, few studies have investigated whether viral stabilization could occur in this niche. Here, we address this question by investigating influenza A virus stabilization by a range of commensal bacteria in systems representing respiratory aerosols and droplets.

[Ballistic injury, decaying wounds: the nurse at the heart of the long rehabilitation process]. / Lésion balistique, plaies délabrantes : l'infirmier au cœur du long parcours de réhabilitation.

Ballistic injuries are disabling. Its functional impact is determined by its trajectory. Whether the injury affects a limb that could jeopardize its preservation, visceral lesions or craniocerebral and vertebro-medullary wounds, the nurse is at the heart of multidisciplinary care to limit and compensate for the after-effects. Directed healing, appropriate analgesia, settling in, technical training for this new, modified body (stoma, self-catheterization, appliances, etc.) and support in accepting the injury are all part of the nurse's role in helping the injured person rebuild his or her life.

The neuraminidase activity of influenza A virus determines the strain-specific sensitivity to neutralization by respiratory mucus.

IMPORTANCE: The respiratory tract of humans is constantly exposed to potentially harmful agents, such as small particles or pathogens, and thus requires protective measures. Respiratory mucus that lines the airway epithelia plays a major role in the prevention of viral infections by limiting the mobility of viruses, allowing subsequent mucociliary clearance. Understanding the interplay between respiratory mucus and viruses can help elucidate host and virus characteristics that enable the initiation of infection. Here, we tested a panel of primary influenza A viruses of avian or human origin for their sensitivity to mucus derived from primary human airway cultures and found that differences between virus strains can be mapped to viral neuraminidase activity. We also show that binding of influenza A viruses to decoy receptors on highly glycosylated mucus components constitutes the major inhibitory function of mucus against influenza A viruses.

Inactivation mechanisms of influenza A virus under pH conditions encountered in aerosol particles as revealed by whole-virus HDX-MS.

Multiple respiratory viruses, including influenza A virus (IAV), can be transmitted via expiratory aerosol particles, and aerosol pH was recently identified as a major factor influencing airborne virus infectivity. Indoors, small exhaled aerosols undergo rapid acidification to pH ~4. IAV is known to be sensitive to mildly acidic conditions encountered within host endosomes; however, it is unknown whether the same mechanisms could mediate viral inactivation within the more acidic aerosol micro-environment. Here, we identified that transient exposure to pH 4 caused IAV inactivation by a two-stage process, with an initial sharp decline in infectious titers mainly attributed to premature attainment of the post-fusion conformation of viral protein haemagglutinin (HA). Protein changes were observed by hydrogen-deuterium exchange coupled to mass spectrometry (HDX-MS) as early as 10 s post-exposure to acidic conditions. Our HDX-MS data are in agreement with other more labor-intensive structural analysis techniques, such as X-ray crystallography, highlighting the ease and usefulness of whole-virus HDX-MS for multiplexed protein analyses, even within enveloped viruses such as IAV. Additionally, virion integrity was partially but irreversibly affected by acidic conditions, with a progressive unfolding of the internal matrix protein 1 (M1) that aligned with a more gradual decline in viral infectivity with time. In contrast, no acid-mediated changes to the genome or lipid envelope were detected. Improved understanding of respiratory virus fate within exhaled aerosols constitutes a global public health priority, and information gained here could aid the development of novel strategies to control the airborne persistence of seasonal and/or pandemic influenza in the future. IMPORTANCE It is well established that COVID-19, influenza, and many other respiratory diseases can be transmitted by the inhalation of aerosolized viruses. Many studies have shown that the survival time of these airborne viruses is limited, but it remains an open question as to what drives their infectivity loss. Here, we address this question for influenza A virus by investigating structural protein changes incurred by the virus under conditions relevant to respiratory aerosol particles. From prior work, we know that expelled aerosols can become highly acidic due to equilibration with indoor room air, and our results indicate that two viral proteins are affected by these acidic conditions at multiple sites, leading to virus inactivation. Our findings suggest that the development of air treatments to quicken the speed of aerosol acidification would be a major strategy to control infectious bioburdens in the air.

Expiratory Aerosol pH: The Overlooked Driver of Airborne Virus Inactivation.

Respiratory viruses, including influenza virus and SARS-CoV-2, are transmitted by the airborne route. Air filtration and ventilation mechanically reduce the concentration of airborne viruses and are necessary tools for disease mitigation. However, they ignore the potential impact of the chemical environment surrounding aerosolized viruses, which determines the aerosol pH. Atmospheric aerosol gravitates toward acidic pH, and enveloped viruses are prone to inactivation at strong acidity levels. Yet, the acidity of expiratory aerosol particles and its effect on airborne virus persistence have not been examined. Here, we combine pH-dependent inactivation rates of influenza A virus (IAV) and SARS-CoV-2 with microphysical properties of respiratory fluids using a biophysical aerosol model. We find that particles exhaled into indoor air (with relative humidity ≥ 50%) become mildly acidic (pH ∼ 4), rapidly inactivating IAV within minutes, whereas SARS-CoV-2 requires days. If indoor air is enriched with nonhazardous levels of nitric acid, aerosol pH drops by up to 2 units, decreasing 99%-inactivation times for both viruses in small aerosol particles to below 30 s. Conversely, unintentional removal of volatile acids from indoor air may elevate pH and prolong airborne virus persistence. The overlooked role of aerosol acidity has profound implications for virus transmission and mitigation strategies.

Sec61 Inhibitor Apratoxin S4 Potently Inhibits SARS-CoV-2 and Exhibits Broad-Spectrum Antiviral Activity.

There is a pressing need for host-directed therapeutics that elicit broad-spectrum antiviral activities to potentially address current and future viral pandemics. Apratoxin S4 (Apra S4) is a potent Sec61 inhibitor that prevents cotranslational translocation of secretory proteins into the endoplasmic reticulum (ER), leading to anticancer and antiangiogenic activity both in vitro and in vivo. Since Sec61 has been shown to be an essential host factor for viral proteostasis, we tested Apra S4 in cellular models of viral infection, including SARS-CoV-2, influenza A virus, and flaviviruses (Zika, West Nile, and Dengue virus). Apra S4 inhibited viral replication in a concentration-dependent manner and had high potency particularly against SARS-CoV-2 and influenza A virus, with subnanomolar activity in human cells. Characterization studies focused on SARS-CoV-2 revealed that Apra S4 impacted a post-entry stage of the viral life-cycle. Transmission electron microscopy revealed that Apra S4 blocked formation of stacked double-membrane vesicles, the sites of viral replication. Apra S4 reduced dsRNA formation and prevented viral protein production and trafficking of secretory proteins, especially the spike protein. Given the potent and broad-spectrum activity of Apra S4, further preclinical evaluation of Apra S4 and other Sec61 inhibitors as antivirals is warranted.

Phosphoproteomic profiling of influenza virus entry reveals infection-triggered filopodia induction counteracted by dynamic cortactin phosphorylation.

Binding of influenza virus to its receptor triggers signaling cascades that reprogram the cell for infection. To elucidate global virus-induced changes to the cellular signaling landscape, we conducted a quantitative phosphoproteomic screen with human and avian influenza viruses. Proteins with functions in cell adhesion and cytoskeletal remodeling are overrepresented among the hits, and the majority of factors undergoing phosphorylation changes have a significant impact on infection efficiency. We show that influenza virus induces the formation of filopodia through Cdc42 signaling, which results in enhanced virus endocytosis. The host cell counteracts this mechanism with cortactin, a regulator of actin polymerization that becomes phosphorylated in response to virus binding and translocates to the cell cortex, where it limits filopodia formation and virus uptake. Overall, our study reveals the signaling cascades induced by influenza virus receptor engagement and uncovers virus-induced filopodia formation that is counteracted by the host cell.

Combined computational and cellular screening identifies synergistic inhibition of SARS-CoV-2 by lenvatinib and remdesivir.

Rapid repurposing of existing drugs as new therapeutics for COVID-19 has been an important strategy in the management of disease severity during the ongoing SARS-CoV-2 pandemic. Here, we used high-throughput docking to screen 6000 compounds within the DrugBank library for their potential to bind and inhibit the SARS-CoV-2 3 CL main protease, a chymotrypsin-like enzyme that is essential for viral replication. For 19 candidate hits, parallel in vitro fluorescence-based protease-inhibition assays and Vero-CCL81 cell-based SARS-CoV-2 replication-inhibition assays were performed. One hit, diclazuril (an investigational anti-protozoal compound), was validated as a SARS-CoV-2 3 CL main protease inhibitor in vitro (IC50 value of 29 µM) and modestly inhibited SARS-CoV-2 replication in Vero-CCL81 cells. Another hit, lenvatinib (approved for use in humans as an anti-cancer treatment), could not be validated as a SARS-CoV-2 3 CL main protease inhibitor in vitro, but serendipitously exhibited a striking functional synergy with the approved nucleoside analogue remdesivir to inhibit SARS-CoV-2 replication, albeit this was specific to Vero-CCL81 cells. Lenvatinib is a broadly-acting host receptor tyrosine kinase (RTK) inhibitor, but the synergistic effect with remdesivir was not observed with other approved RTK inhibitors (such as pazopanib or sunitinib), suggesting that the mechanism-of-action is independent of host RTKs. Furthermore, time-of-addition studies revealed that lenvatinib/remdesivir synergy probably targets SARS-CoV-2 replication subsequent to host-cell entry. Our work shows that combining computational and cellular screening is a means to identify existing drugs with repurposing potential as antiviral compounds. Future studies could be aimed at understanding and optimizing the lenvatinib/remdesivir synergistic mechanism as a therapeutic option.

An antiviral trap made of protein nanofibrils and iron oxyhydroxide nanoparticles.

Minimizing the spread of viruses in the environment is the first defence line when fighting outbreaks and pandemics, but the current COVID-19 pandemic demonstrates how difficult this is on a global scale, particularly in a sustainable and environmentally friendly way. Here we introduce and develop a sustainable and biodegradable antiviral filtration membrane composed of amyloid nanofibrils made from food-grade milk proteins and iron oxyhydroxide nanoparticles synthesized in situ from iron salts by simple pH tuning. Thus, all the membrane components are made of environmentally friendly, non-toxic and widely available materials. The membrane has outstanding efficacy against a broad range of viruses, which include enveloped, non-enveloped, airborne and waterborne viruses, such as SARS-CoV-2, H1N1 (the influenza A virus strain responsible for the swine flu pandemic in 2009) and enterovirus 71 (a non-enveloped virus resistant to harsh conditions, such as highly acidic pH), which highlights a possible role in fighting the current and future viral outbreaks and pandemics.

Experimental characterization of the moment-angle curve during level and slope locomotion of transtibial amputee: Which parameters can be extracted to quantify the adaptations of microprocessor prosthetic ankle?

In case of transtibial amputation, the deficit resulting from the loss of the lower limb can be partly compensated with a prosthetic foot and adapted rehabilitation. New prosthetic feet have been developed for transtibial amputees to mimic ankle adaptability to varying terrain. Among them, Microprocessor Prosthetic Ankles (MPA) have a microprocessor to control an electric or a hydraulic actuator to adapt ankle kinematics in stairs and slopes. The objective is to investigate parameters extracted from the moment-angle curve (MAC) and use them to compare 3 MPA during level and slope locomotion against energy storing and return (ESR) foot. Five persons with lower limb transtibial amputation successively fitted with 3 MPA (Propriofoot™, Elan™, Meridium™) compared to their ESR foot. The participants had 2 weeks of adaptation before data acquisition and then a 3 week wash-out period. Range of motion, equilibrium point, hysteresis, late stance energy released, and quasi-stiffness were computed on level ground and 12% slope (upward and downward) thanks to the MAC at the ankle. The study shows the relevance of MAC parameters to evaluate the behavior of MPA. In particular, compared to ESR, all MPA tested in the present study demonstrated a better angle adaptation between walking conditions but a decrease of available energy for the propulsion. Among MPA, main results were: (i) for the Propriofoot™: an adaptation of the ankle angle without modification of the pattern of the MAC (ii) for the Elan™: a limited adaptation of the range of motion but a modification of the energy released (iii) for the Meridium™, the highest adaptation of the range of motion but the lowest available energy of propulsion. One of the main findings of the research is to show and quantify the relationship between range of motion and energy available when using different prosthetic feet in different walking conditions.

SARS-CoV-2 variants reveal features critical for replication in primary human cells.

Since entering the human population, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2; the causative agent of Coronavirus Disease 2019 [COVID-19]) has spread worldwide, causing >100 million infections and >2 million deaths. While large-scale sequencing efforts have identified numerous genetic variants in SARS-CoV-2 during its circulation, it remains largely unclear whether many of these changes impact adaptation, replication, or transmission of the virus. Here, we characterized 14 different low-passage replication-competent human SARS-CoV-2 isolates representing all major European clades observed during the first pandemic wave in early 2020. By integrating viral sequencing data from patient material, virus stocks, and passaging experiments, together with kinetic virus replication data from nonhuman Vero-CCL81 cells and primary differentiated human bronchial epithelial cells (BEpCs), we observed several SARS-CoV-2 features that associate with distinct phenotypes. Notably, naturally occurring variants in Orf3a (Q57H) and nsp2 (T85I) were associated with poor replication in Vero-CCL81 cells but not in BEpCs, while SARS-CoV-2 isolates expressing the Spike D614G variant generally exhibited enhanced replication abilities in BEpCs. Strikingly, low-passage Vero-derived stock preparation of 3 SARS-CoV-2 isolates selected for substitutions at positions 5/6 of E and were highly attenuated in BEpCs, revealing a key cell-specific function to this region. Rare isolate-specific deletions were also observed in the Spike furin cleavage site during Vero-CCL81 passage, but these were rapidly selected against in BEpCs, underscoring the importance of this site for SARS-CoV-2 replication in primary human cells. Overall, our study uncovers sequence features in SARS-CoV-2 variants that determine cell-specific replication and highlights the need to monitor SARS-CoV-2 stocks carefully when phenotyping newly emerging variants or potential variants of concern.

Microprocessor prosthetic ankles: comparative biomechanical evaluation of people with transtibial traumatic amputation during standing on level ground and slope.

BACKGROUND: The compensations occurrence due to the alteration of the posture and the gait of persons with lower limb amputation is still an issue in prosthetic fitting. Recently, prosthetic feet designed to reproduce the physiological behaviour of the ankle using a microprocessor control have been commercialized to address this issue. OBJECTIVES: Investigate the relevance of these microprocessor prosthetic ankles (MPAs) in the ability of standing on both level and inclined surfaces. METHODS: Six persons with transtibial amputation usually fitted with energy storing and returning (ESR) foot tested three MPAs: Elan® Endolite (MPA1), Meridium® Ottobock (MPA2), ProprioFoot® Ossur (MPA3). Each MPA data acquisition was preceded of a 2 weeks adaptation period at home and followed by a 3-weeks wash-out period with their ESR. Lower limb angular position and moment, Centre of Pressure (CoP) position, Ground Reaction Forces (GRF) and functional scores were collected in static, on level ground and 12% inclined slope. RESULTS: MPAs allowed a better posture and a reduction of residual knee moment on positive and/or negative slope compared to ESR. Results also reflect that the MPA2 allows the best control of the CoP in all situations. CONCLUSIONS: An increased ankle mobility is associated with a better posture and balance on slope. Gait analysis would complete these outcomes. CLINICAL RELEVANCE: This study compares three MPAs to ESR analysing static posture. Static analysis on level ground and slope represents the challenging conditions people with amputation have to cope with in their daily life, especially outdoors. Having a better understanding of the three MPAs behaviour could help to adequately fit the prosthesis to each patient. Implications for rehabilitation This is a study comparing three MPAs. The static analysis in standard and constraining conditions (slope) reflects the balance of people with amputation in their daily life, especially outdoors. Having a better understanding of the behaviour of each foot could help to adequately fit the prosthesis to each patient.

Antiviral Activity of Type I, II, and III Interferons Counterbalances ACE2 Inducibility and Restricts SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), is a recently emerged respiratory coronavirus that has infected >23 million people worldwide with >800,000 deaths. Few COVID-19 therapeutics are available, and the basis for severe infections is poorly understood. Here, we investigated properties of type I (ß), II (γ), and III (λ1) interferons (IFNs), potent immune cytokines that are normally produced during infection and that upregulate IFN-stimulated gene (ISG) effectors to limit virus replication. IFNs are already in clinical trials to treat COVID-19. However, recent studies highlight the potential for IFNs to enhance expression of host angiotensin-converting enzyme 2 (ACE2), suggesting that IFN therapy or natural coinfections could exacerbate COVID-19 by upregulating this critical virus entry receptor. Using a cell line model, we found that beta interferon (IFN-ß) strongly upregulated expression of canonical antiviral ISGs, as well as ACE2 at the mRNA and cell surface protein levels. Strikingly, IFN-λ1 upregulated antiviral ISGs, but ACE2 mRNA was only marginally elevated and did not lead to detectably increased ACE2 protein at the cell surface. IFN-γ induced the weakest ISG response but clearly enhanced surface expression of ACE2. Importantly, all IFN types inhibited SARS-CoV-2 replication in a dose-dependent manner, and IFN-ß and IFN-λ1 exhibited potent antiviral activity in primary human bronchial epithelial cells. Our data imply that type-specific mechanisms or kinetics shape IFN-enhanced ACE2 transcript and cell surface levels but that the antiviral action of IFNs against SARS-CoV-2 counterbalances any proviral effects of ACE2 induction. These insights should aid in evaluating the benefits of specific IFNs, particularly IFN-λ, as repurposed therapeutics.IMPORTANCE Repurposing existing, clinically approved, antiviral drugs as COVID-19 therapeutics is a rapid way to help combat the SARS-CoV-2 pandemic. Interferons (IFNs) usually form part of the body's natural innate immune defenses against viruses, and they have been used with partial success to treat previous new viral threats, such as HIV, hepatitis C virus, and Ebola virus. Nevertheless, IFNs can have undesirable side effects, and recent reports indicate that IFNs upregulate the expression of host ACE2 (a critical entry receptor for SARS-CoV-2), raising the possibility that IFN treatments could exacerbate COVID-19. Here, we studied the antiviral- and ACE2-inducing properties of different IFN types in both a human lung cell line model and primary human bronchial epithelial cells. We observed differences between IFNs with respect to their induction of antiviral genes and abilities to enhance the cell surface expression of ACE2. Nevertheless, all the IFNs limited SARS-CoV-2 replication, suggesting that their antiviral actions can counterbalance increased ACE2.

Breaking the Convention: Sialoglycan Variants, Coreceptors, and Alternative Receptors for Influenza A Virus Entry.

The influenza A virus (IAV) envelope protein hemagglutinin binds α2,6- or α2,3-linked sialic acid as a host cell receptor. Bat IAV subtypes H17N10 and H18N11 form an exception to this rule and do not bind sialic acid but enter cells via major histocompatibility complex (MHC) class II. Here, we review current knowledge on IAV receptors with a focus on sialoglycan variants, protein coreceptors, and alternative receptors that impact IAV attachment and internalization beyond the well-described sialic acid binding.

[Severe burns, a long journey of care and rehabilitation]. / Le brûlé grave, un long parcours de soins et de réhabilitation.

At the patient's bedside 24 hours a day, the nurse is at the heart of the rehabilitation management of the severely burnt patient: installation, technical dressings, supervision of postures and placement of compressors, to limit the functional consequences to the type of retractable and hypertrophic scars. The nurse takes care of the patient in this long journey leading to social reintegration; from accompaniment to autonomy and acceptance of self-image.

Spinopelvic sagittal alignment of patients with transfemoral amputation.

PURPOSE: This study aims to describe the spinopelvic sagittal alignment in transfemoral amputees (TFAs) from a radiologic study of the spine with a postural approach to better understand the high prevalence of low back pain (LBP) in this population. METHODS: TFAs underwent X-rays with 3-D reconstructions of the full spine and pelvis. Sagittal parameters were analyzed and compared to the literature. Differences between TFAs with and without LBP were also observed. RESULTS: Twelve subjects have been prospectively included (TFA-LBP group (n = 5) and TFA-NoP group (n = 7)). Four of the five subjects of the TFA-LBP group and two of the seven in TFAs-NoP group had an imbalanced sagittal posture, especially regarding the T9-tilt, significantly higher in the TFA-LBP group than in the TFA-NoP (p = 0.046). Eight subjects (6 TFA-NoP and 2 TFA-LBP) had abnormal low value of thoracic kyphosis (TK). Moreover, the mean angle of TK in the TFA-NoP group was lower than in the TFA-LBP group (p = 0.0511). CONCLUSION: In the considered sample, TFAs often present a sagittal imbalance. A low TK angle seems to be associated with the absence of LBP. It can be hypothesized that this compensatory mechanism of the sagittal imbalance is the most accessible in this population. This study emphasizes the importance of considering the sagittal balance of the pelvis and the spine in patients with a TFA to better understand the high prevalence of LBP in this population. It should be completed by the analysis of the spinopelvic balance and the lower limbs in 3D. These slides can be retrieved under Electronic Supplementary Material.

MHC class II proteins mediate cross-species entry of bat influenza viruses.

Zoonotic influenza A viruses of avian origin can cause severe disease in individuals, or even global pandemics, and thus pose a threat to human populations. Waterfowl and shorebirds are believed to be the reservoir for all influenza A viruses, but this has recently been challenged by the identification of novel influenza A viruses in bats1,2. The major bat influenza A virus envelope glycoprotein, haemagglutinin, does not bind the canonical influenza A virus receptor, sialic acid or any other glycan1,3,4, despite its high sequence and structural homology with conventional haemagglutinins. This functionally uncharacterized plasticity of the bat influenza A virus haemagglutinin means the tropism and zoonotic potential of these viruses has not been fully determined. Here we show, using transcriptomic profiling of susceptible versus non-susceptible cells in combination with genome-wide CRISPR-Cas9 screening, that the major histocompatibility complex class II (MHC-II) human leukocyte antigen DR isotype (HLA-DR) is an essential entry determinant for bat influenza A viruses. Genetic ablation of the HLA-DR α-chain rendered cells resistant to infection by bat influenza A virus, whereas ectopic expression of the HLA-DR complex in non-susceptible cells conferred susceptibility. Expression of MHC-II from different bat species, pigs, mice or chickens also conferred susceptibility to infection. Notably, the infection of mice with bat influenza A virus resulted in robust virus replication in the upper respiratory tract, whereas mice deficient for MHC-II were resistant. Collectively, our data identify MHC-II as a crucial entry mediator for bat influenza A viruses in multiple species, which permits a broad vertebrate tropism.

[The nurse and the reconstruction of military casualties through sport]. / L'infirmière et la reconstruction du blessé militaire par le sport.

Soldiers are confronted with physical and mental injuries which constitute a social trauma. The French army has put in place tools, notably sports courses, to favour resilience and the reintegration of casualties. Nurses and nurse assistants working in physical medicine and rehabilitation and psychiatry, play a key role using their skills to support this scheme which runs outside the hospital setting.