André Léo journaliste. Engagement et témoignage (1866-1871)

L’article propose une contribution à l’histoire du journalisme au xixe siècle à travers le corpus d’un auteur, André Léo, c’est-à-dire Léodile Champseix, née Béra (1824-1900), longtemps oubliée mais aujourd’hui reconnue comme une des voix majeures du féminisme et du socialisme des années 1860 et 1870. S’intéresser à ce corpus, c’est prendre la mesure de l’importance de la presse comme support de l’engagement politique mais aussi comme enjeu d’écriture pour les écrivains du second xixe siècle. Car si le journalisme de reportage n’est pas encore défini comme tel et instauré en modèle dominant, la presse est bien, dès la fin du Second Empire, le vecteur privilégié d’une littérature de témoignage, étroitement articulée au cours des événements et parfois aux urgences de l’heure, comme le montre en particulier le journalisme communard tel que le pratiqua André Léo

Recombinant retrovirus-like particle forming DNA vaccines in prime-boost immunization and their use for hepatitis C virus vaccine development.

International audienceBACKGROUND: The expression of Moloney murine leukemia virus (Mo-MLV) gag proteins is sufficient to generate retrovirus-like particles (retroVLPs) that can be used as antigen-display platforms by pseudotyping with heterologous envelope proteins or by insertion of epitopes in structural constituents. To circumvent the in vitro production of such retroVLPs, we used DNA plasmids generating recombinant retroVLPs (plasmo-retroVLPs) as immunogens. We previously demonstrated that plasmo-retroVLPs induce significantly better antigen-specific T cell responses and antiviral immune protection than plasmids bearing a single mutation preventing retroVLPs assembly. In the present study, we investigated the possibility of using such plasmo-retroVLPs in prime-boost immunization strategies for hepatitis C virus (HCV) vaccine development. METHODS: To define the best immunization regimen with plasmo-retroVLPs and serotype 5 recombinant adenovirus vectors (rAd5), we used standardized methodologies measuring immune responses to the GP(33-41) 'gold standard' antigen. The protective efficacy of these immunization schedules was also evaluated in mice after tumor challenge. We then applied the optimal prime-boost immunization strategy using vectors expressing HCV-E1/E2 envelope glycoproteins. RESULTS: Using vectors expressing the model antigen, we demonstrated that rAd5(GP33-41)/plasmo-retroVLP(GP33-41) regimen induced significantly higher cellular immune responses than plasmo-retroVLP(GP33-41)/rAd5(GP33-41). Consequently, HCV-specific plasmo-retroVLPs (plasmo-retroVLP(E1E2)) were used as boost in mice primed with rAd5(E1E2) and we observed that plasmo-retroVLP(E1E2) significantly increased E1/E2-specific interferon-gamma cellular responses and E2-specific antibody generation. By contrast, plasmids unable to form E1/E2-pseudotyped retroVLPs had no boosting effect, revealing the importance of presenting E1/E2 in a particulate form. CONCLUSIONS: Altogether, combining plasmo-retroVLPs that represent a new class of genetic vaccines in a heterologous prime-boost vaccination strategy appears to be a promising strategy for HCV vaccine development

Kinases required in hepatitis C virus entry and replication highlighted by small interference RNA screening.

International audienceThe entry pathway of the hepatitis C virus (HCV), a major human pathogen, into the cell is incompletely defined. To better characterize this viral life cycle stage, we screened a small interfering RNA library dedicated to the membrane trafficking and remodeling with the infection model of Huh-7.5.1 cells by HCV pseudoparticles (HCVpp). Results showed that the down-regulation of different factors implied in clathrin-mediated endocytosis (CME) inhibits HCVpp cell infection. In addition, knockdown of the phosphatidylinositol 4-kinase type III-alpha (PI4KIIIalpha) prevented infection by HCVpp or by cell-culture grown JFH-1-based HCV. Moreover, the replication activity of an HCV replicon was also affected by the PI4KIIIalpha knockdown. Additional investigations on the different members of the PI4K family revealed that the presence of PI4KIIIbeta in the host cells influenced their susceptibility to HCVpp infection and their capacity to sustain the HCV replication. The PI4KIII involvement during the HCV life cycle seemed to occur by other ways than the control of the CME or of the membranous expression of HCV receptors. Finally, our library screening completed data on the CME-dependant entry route of HCV and identified 2 kinases, PI4KIIIalpha and beta, as relevant potential therapeutic targets

Hepatitis D virus interferes with hepatitis B virus RNA production via interferon-dependent and -independent mechanisms

International audienceBackground & Aims: Chronic co-infection with hepatitis B and D viruses (HBV and HDV) leads to the most aggressive form of chronic viral hepatitis. Here, we aimed at elucidating the molecular mechanisms leading to the interference of HDV on HBV observed in most co-infected patients.Methods: Patient liver tissues, primary human hepatocytes, HepaRG cells and human liver chimeric mice were used to analyze the effect of HDV on HBV using virological and RNA-seq analyses, as well as RNA synthesis, stability and association assays.Results: Transcriptomic analyses in cell culture and mouse models of co-infection allowed to define the HDV-induced signature mainly composed of interferon (IFN)-stimulated genes (ISGs). We also provide evidence that ISGs are upregulated in HDV-HBV chronically infected patients but not in cells only expressing the HDV antigens (HDAg). Inhibition of the hepatocyte IFN response partially rescued the levels of HBV parameters. We observed less HBV RNAs synthesis upon HDV infection or HDV protein expression. Additionally, HDV infection or expression of HDAg alone specifically accelerated the decay of HBV RNAs and HDAg are associated with HBV RNAs. On the contrary, HDAg expression did not affect other viruses such as hepatitis C virus (HCV) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Conclusions: Our data indicate that HDV interferes with HBV through both IFN-dependent and IFN-independent mechanisms. Specifically, we uncover a new viral interference mechanism in which proteins of a satellite virus affect RNA production of its helper virus. Exploiting these finding could pave the way to the development of new therapeutic strategies against HBV

Hepatitis D virus interferes with hepatitis B virus RNA production via interferon-dependent and -independent mechanisms

International audienceBackground & Aims: Chronic co-infection with hepatitis B and D viruses (HBV and HDV) leads to the most aggressive form of chronic viral hepatitis. Here, we aimed at elucidating the molecular mechanisms leading to the interference of HDV on HBV observed in most co-infected patients.Methods: Patient liver tissues, primary human hepatocytes, HepaRG cells and human liver chimeric mice were used to analyze the effect of HDV on HBV using virological and RNA-seq analyses, as well as RNA synthesis, stability and association assays.Results: Transcriptomic analyses in cell culture and mouse models of co-infection allowed to define the HDV-induced signature mainly composed of interferon (IFN)-stimulated genes (ISGs). We also provide evidence that ISGs are upregulated in HDV-HBV chronically infected patients but not in cells only expressing the HDV antigens (HDAg). Inhibition of the hepatocyte IFN response partially rescued the levels of HBV parameters. We observed less HBV RNAs synthesis upon HDV infection or HDV protein expression. Additionally, HDV infection or expression of HDAg alone specifically accelerated the decay of HBV RNAs and HDAg are associated with HBV RNAs. On the contrary, HDAg expression did not affect other viruses such as hepatitis C virus (HCV) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Conclusions: Our data indicate that HDV interferes with HBV through both IFN-dependent and IFN-independent mechanisms. Specifically, we uncover a new viral interference mechanism in which proteins of a satellite virus affect RNA production of its helper virus. Exploiting these finding could pave the way to the development of new therapeutic strategies against HBV

A recurrent activating missense mutation in Waldenström macroglobulinemia affects the DNA binding of the ETS transcription factor SPI1 and enhances proliferation

The ETS-domain transcription factors divide into subfamilies based on protein similarities, DNA binding sequences and interaction with cofactors. They are regulated by extracellular clues and contribute to cellular processes, including proliferation and transformation. ETS genes are targeted through genomic rearrangements in oncogenesis. The PU.1/SPI1 gene is inactivated by point mutations in human myeloid malignancies. We identified a recurrent somatic mutation (Q226E) in PU.1/SPI1 in Waldenstrom macroglobulinemia, a B-cell lymphoproliferative disorder. It affects the DNA binding affinity of the protein and allows the mutant protein to bind and activate more frequently promoter regions with respect to wild type protein. Mutant SPI1 binding at promoters activates gene-sets typically promoted by other ETS factors, resulting in enhanced proliferation and decreased terminal B-cell differentiation in model cell lines and primary samples. In summary, we describe oncogenic subversion of transcription factor function through subtle alteration of DNA binding leading to cellular proliferation and differentiation arrest

Women’s dissatisfaction with inappropriate behavior by health care workers during childbirth care in France: A survey study

Background As part of a decades-long process of restructuring primary care, independent (also known as community) healthcare workers are being encouraged to work in groups to facilitate their coordination and continuity of care in France. French independent midwives perform about half of the early prenatal interviews that identify mothers' needs during pregnancy and then refer them to the appropriate resources. The French government, however, structured the COVID-19 pandemic response around public health institutions and did not directly mobilise these community healthcare workers during the lockdown phase. These responses have raised questions about their role within the healthcare system in crises. This survey’s main objectives were to estimate the proportion of independent midwives who experienced new difficulties in referring women to healthcare facilities or other caregivers and in collaborating with hospitals during the first stage of this pandemic. The secondary objective was to estimate the proportion, according to their mode of practice, of independent midwives who considered that all the women under their care had risked harm due to failed or delayed referral to care. Methods We conducted an online national survey addressed to independent midwives in France from 29 April to 15 May 2020, around the end of the first lockdown (17 March–11 May, 2020). Results Of the 5264 registered independent midwives in France, 1491 (28.3%) responded; 64.7% reported new or greater problems during the pandemic in referring women to health facilities or care-providers, social workers in particular, and 71.0% reported new difficulties collaborating with hospitals. Nearly half (46.2%) the respondents considered that all the women in their care had experienced, to varying degrees, a lack of or delay in care that could have affected their health. This proportion did not differ according to the midwives’ form of practice: solo practice, group practice with other midwives only, or group practice with at least two types of healthcare professionals. Conclusions The pandemic has degraded the quality of pregnant women’s care in France and challenged the French model of care, which is highly compartmentalised between an almost exclusively independent primary care (community) sector and a predominantly salaried secondary care (hospital) sector