Ebola et Marburg : les hommes contre-attaquent

La fréquence des épidémies de fièvres hémorragiques à virus Ebola ou Marburg constatée en Afrique Centrale est en augmentation depuis une dizaine d’années. Une vigilance accrue permet de détecter très précocement la plupart de ces épidémies, mais une quarantaine stricte reste le seul moyen de lutter contre ces virus : en effet, il n’existe à ce jour ni vaccin, ni traitement utilisable chez l’homme, même si la recherche progresse. Cet article fait le point sur deux résultats récents. Le premier est la découverte du mécanisme par lequel la glycoprotéine de surface du virus Ebola est activée pour réaliser la fusion des membranes virale et cellulaire : il s’agit d’un clivage protéolytique médié par des protéases endosomales, et cette découverte pourrait avoir des applications thérapeutiques. Le second résultat concerne la réussite d’essais vaccinaux chez le singe, un succès encourageant pour le développement de vaccins chez l’homme.Ebola and Marburg viruses are the causative agents of rapidly progressive hemorrhagic fevers with high mortality rates. Pre- or post-exposure treatments against the diseases are currently not available for human use. In the field, establishment of strict quarantine measures preventing further virus transmission are still the only way to fight the infections. However, our knowledge of Ebola and Marburg viruses has markedly increased as a result of two recent discoveries discussed in this review. Chandran et al. have elucidated the mechanism by which Ebola GP is converted to a fusion-active form. Infectivity of Ebola virus was shown to be dependent on the cleavage of GP by cellular endosomal proteases, cathepsin B and L, thus opening new therapeutic approaches options. As for Jones SM et al., they have successfully vaccinated monkeys with recombinant vesicular stomatitis virus expressing Ebola or Marburg virus surface glycoprotein GP, a promising vaccine approach

Impact of the 2009 influenza A(H1N1) pandemic wave on the pattern of hibernal respiratory virus epidemics, France, 2009.

International audienceThis short report based on clinical surveillance and laboratory data describes the circulation of rhinoviruses, influenza viruses and respiratory syncytial viruses (RSV) in France during the 2009-10 season compared with the previous winter season. The delayed circulation of RSV observed in 2009-10 compared with 2008-09 suggests that the early circulation of the 2009 pandemic influenza A(H1N1) viruses had an impact on the RSV epidemic

Ces virus qui nous habitent et qui nous visitent : le virome humain

Les progrès récents des nouvelles techniques de séquençage ont ouvert la voie au décryptage du virome humain qui peut être défini comme l’ensemble de tous les virus présents dans le corps humain. Ces virus sont de différents types : endogènes, procaryotes, archéaux et eucaryotes

Ebola et Marburg : les homes contre-attaquent

La fréquence des épidémies de fièvres hémorragiques à virus Ebola ou Marburg constatée en Afrique Centrale est en augmentation depuis une dizaine d’années. Une vigilance accrue permet de détecter très précocement la plupart de ces épidémies, mais une quarantaine stricte reste le seul moyen de lutter contre ces virus : en effet, il n’existe à ce jour ni vaccin, ni traitement utilisable chez l’homme, même si la recherché progresse. Cet article fait le point sur deux resultants récents. Le premier est la découverte du mécanisme par lequel la glycoprotéine de surface du virus Ebola est activée pour réaliser la fusion des membranes virale et cellulaire : il s’agit d’un clivage protéolytique médié par des proteases endosomales, et cette découverte pourrait avoir des applications thérapeutiques. Le second résultat concerne la réussite d’essais vaccinaux chez le singe, un succès encourageant pour le développement de vaccins chez l’homme

Preimplantation genetic diagnosis in donkey embryos after biopsy

International audienc

Synergistic Effects of Influenza and Staphylococcus aureus Toxins on Inflammation Activation and Cytotoxicity in Human Monocytic Cell Lines

International audienceIn patients with influenza, morbidity and mortality are strongly influenced by infections with Staphylococcus aureus producing high amounts of certain toxins. Here we tested the impact of influenza virus on the pro-inflammatory and cytotoxic actions of a panel of S. aureus virulence factors, including Panton-Valentine Leucocidin (PVL), phenol-soluble modulin α1 (PSMα1) and 3 (PSMα3), α-hemolysin (Hla), and cell wall components, i.e., heat-killed S. aureus (HKSA) and protein A. We initially screened for potential synergic interactions using a standardized in vitro model in influenza-infected continuous human monocytic cell lines. Then we tested the identified associations using an ex vivo model in influenza-infected human monocytes freshly isolated from blood. Co-exposure to influenza virus and HKSA, PVL, PSMα1, and PSMα3 increased NF-\kappaB/AP-1 pathway activation in THP1-XBlue cells, and co-exposure to influenza virus and PVL increased cytotoxicity in U937 cells. In monocytes isolated from blood, the synergy between influenza virus and HKSA was confirmed based on cytokine production (TNF-α, IL-1β, IL-6), and co-exposure to influenza virus and Hla-increased cytotoxicity. Our findings suggest that influenza virus potentiates the pro-inflammatory action of HKSA and contributes to the cytotoxicity of Hla on monocytes. Synergic interactions identified in the cell-line model must be cautiously interpreted since few were relevant in the ex vivo model

Duck pluripotent stem cells and their susceptibility to influenza virus

Tremendous efforts have been made to derive embryonic stem cells (ESC) from various species, primarily in mammals. Developing these cell types with self-renewal and differentiation capacities in avian species presents a double interest: 1) fundamental, to study early development and to decipher the mechanisms involved in the maintenance of pluripotency in vitro. 2) biotechnological, to analyze viral replication and to produce specific vaccines instead of using embryonated eggs. So far, only chicken ESC lines and one proprietary duck ESC line have been established and all of them were derived in the presence of serum. The small number of available stem cell lines limits the possibility of comparing avian species among themselves and with mammalian species. Their derivation in media containing serum decreases their potential use for pharmaceutical or veterinary purposes. We have therefore chosen to derive, in chemically defined media, new cell lines from stage X Pekin duck embryos. We have established different independent isolates which can be established in long term culture. The cells maintain the transcriptional signature such as OCT4, NANOG, TERT and ALPL gene transcription and physiological markers of ESC (telomerase activity, Alkaline phosphatase activity) and plasticity of differentiation. These populations then share most of the characteristics expected of pluripotent stem cells (PSCs). Therefore, these new duck PSCs can provide a working basis to analyze the mechanisms of maintenance of pluripotency in avian species by comparing them with already existing chicken cells.Moreover, It has been shown that certain endogenous retroviral elements, usually silent in most cell types, can be transcriptionally reactivated in pluripotent cells. This property remains a major drawback for their use as a substrate for the production of human and veterinary vaccines. We therefore analyzed the activity of reverse transcriptase in the supernatant of different chicken and duck cell lines. We have shown that the new duck ES lines exhibit a very low RT activity, 3 log below the activities measured in the chicken ES cell lines. We then tested the susceptibility of these duck ES cells to influenza viruses. We have shown that duck ES cells, but not duck embryonic fibroblasts, can replicate both human or avian influenza viruses as much as chicken ES cells. These Duck stem cells can therefore be a perfect substrate for producing vaccines under greater safety conditions than those with chicken embryos

Duck pluripotent stem cells and their susceptibility to influenza virus

Tremendous efforts have been made to derive embryonic stem cells (ESC) from various species, primarily in mammals. Developing these cell types with self-renewal and differentiation capacities in avian species presents a double interest: 1) fundamental, to study early development and to decipher the mechanisms involved in the maintenance of pluripotency in vitro. 2) biotechnological, to analyze viral replication and to produce specific vaccines instead of using embryonated eggs. So far, only chicken ESC lines and one proprietary duck ESC line have been established and all of them were derived in the presence of serum. The small number of available stem cell lines limits the possibility of comparing avian species among themselves and with mammalian species. Their derivation in media containing serum decreases their potential use for pharmaceutical or veterinary purposes. We have therefore chosen to derive, in chemically defined media, new cell lines from stage X Pekin duck embryos. We have established different independent isolates which can be established in long term culture. The cells maintain the transcriptional signature such as OCT4, NANOG, TERT and ALPL gene transcription and physiological markers of ESC (telomerase activity, Alkaline phosphatase activity) and plasticity of differentiation. These populations then share most of the characteristics expected of pluripotent stem cells (PSCs). Therefore, these new duck PSCs can provide a working basis to analyze the mechanisms of maintenance of pluripotency in avian species by comparing them with already existing chicken cells.Moreover, It has been shown that certain endogenous retroviral elements, usually silent in most cell types, can be transcriptionally reactivated in pluripotent cells. This property remains a major drawback for their use as a substrate for the production of human and veterinary vaccines. We therefore analyzed the activity of reverse transcriptase in the supernatant of different chicken and duck cell lines. We have shown that the new duck ES lines exhibit a very low RT activity, 3 log below the activities measured in the chicken ES cell lines. We then tested the susceptibility of these duck ES cells to influenza viruses. We have shown that duck ES cells, but not duck embryonic fibroblasts, can replicate both human or avian influenza viruses as much as chicken ES cells. These Duck stem cells can therefore be a perfect substrate for producing vaccines under greater safety conditions than those with chicken embryos

The NS Segment of H1N1pdm09 Enhances H5N1 Pathogenicity in a Mouse Model of Influenza Virus Infections

In 2009, the co-circulation of H5N1 and H1N1pdm09 raised concerns that a reassortment event may lead to highly pathogenic influenza strains. H1N1pdm09 and H5N1 are able to infect the same target cells of the lower respiratory tract. To investigate the capacity of the emergence of reassortant viruses, we characterized viruses obtained from the co-infection of cells with H5N1 (A/Turkey/13/2006) and H1N1pdm09 (A/Lyon/969/2009 H1N1). In our analysis, all the screened reassortants possessed the PB2, HA, and NP segments from H5N1 and acquired one or two of the H1N1pdm09 segments. Moreover, the in vivo infections showed that the acquisition of the NS segment from H1N1pdm09 increased the virulence of H5N1 in mice. We conclude, therefore, that reassortment can occur between these two viruses, even if this process has never been detected in nature