Hemostasis defects underlying the hemorrhagic syndrome caused by mammarenaviruses in a cynomolgus macaque model.

Viral hemorrhagic fevers (HF) are a group of acute febrile diseases with high mortality rates. Although hemostatic dysfunction appears to be a major determinant of the severity of the disease, it is still unclear what pathogenic mechanisms lead to it. In clinical studies it is found that arenaviruses, such as Lassa, Machupo, and Guanarito viruses cause HF that vary in symptoms and biological alterations.

Pathogenesis of recent Lassa virus isolates from lineages II and VII in cynomolgus monkeys.

The area of Lassa virus (LASV) circulation is expanding, with the emergence of highly pathogenic new LASV lineages. Benin recently became an endemic country for LASV and has seen the emergence of a new LASV lineage (VII). The first two outbreaks in 2014 and 2016 showed a relatively high mortality rate compared to other outbreaks.

A single-shot Lassa vaccine induces long-term immunity and protects cynomolgus monkeys against heterologous strains.

A safe and protective Lassa virus vaccine is crucially needed in Western Africa to stem the recurrent outbreaks of Lassa virus infections in Nigeria and the emergence of Lassa virus in previously unaffected countries, such as Benin and Togo. Major challenges in developing a Lassa virus vaccine include the high diversity of circulating strains and their reemergence from 1 year to another. To address each of these challenges, we immunized cynomolgus monkeys with a measles virus vector expressing the Lassa virus glycoprotein and nucleoprotein of the prototypic Lassa virus strain Josiah (MeV-NP).

Early control of viral load by favipiravir promotes survival to Ebola virus challenge and prevents cytokine storm in non-human primates.

Ebola virus has been responsible for two major epidemics over the last several years and there has been a strong effort to find potential treatments that can improve the disease outcome. Antiviral favipiravir was thus tested on non-human primates infected with Ebola virus. Half of the treated animals survived the Ebola virus challenge, whereas the infection was fully lethal for the untreated ones.

Systemic viral spreading and defective host responses are associated with fatal Lassa fever in macaques.

Lassa virus (LASV) is endemic in West Africa and induces a viral hemorrhagic fever (VHF) with up to 30% lethality among clinical cases. The mechanisms involved in control of Lassa fever or, in contrast, the ensuing catastrophic illness and death are poorly understood. We used the cynomolgus monkey model to reproduce the human disease with asymptomatic to mild or fatal disease.

E3 Ligase ITCH Interacts with the Z Matrix Protein of Lassa and Mopeia Viruses and Is Required for the Release of Infectious Particles.

Lassa virus (LASV) and Mopeia virus (MOPV) are two closely related, rodent-born mammarenaviruses. LASV is the causative agent of Lassa fever, a deadly hemorrhagic fever endemic in West Africa, whereas MOPV is non-pathogenic in humans. The Z matrix protein of arenaviruses is essential to virus assembly and budding by recruiting host factors, a mechanism that remains partially defined.

Vaccines inducing immunity to Lassa virus glycoprotein and nucleoprotein protect macaques after a single shot.

Lassa fever is a major threat in Western Africa. The large number of people living at risk for this disease calls for the development of a vaccine against Lassa virus (LASV). We generated live-attenuated LASV vaccines based on measles virus and Mopeia virus platforms and expressing different LASV antigens, with the aim to develop a vaccine able to protect after a single shot.

Autophagy Promotes Infectious Particle Production of Mopeia and Lassa Viruses.

Lassa virus (LASV) and Mopeia virus (MOPV) are two closely related Old-World mammarenaviruses. LASV causes severe hemorrhagic fever with high mortality in humans, whereas no case of MOPV infection has been reported. Comparing MOPV and LASV is a powerful strategy to unravel pathogenic mechanisms that occur during the course of pathogenic arenavirus infection.

Immune parameters and outcomes during Ebola virus disease.

Background: The West African Ebola virus epidemic from 2014-2016 highlighted the lack of knowledge about the pathogenicity of the virus and the factors responsible for outcome. A performant and rapid diagnosis is of crucial importance, as is overcoming the difficulty of providing high-quality patient management during such an extensive outbreak. Here, we propose to study the role of the immune mediators during Ebola virus disease and to define some molecules of importance in the outcome.

Impairment of quality of life in patients with antiphospholipid syndrome.

Objectives: Health-related quality of life (HRQoL) has not been fully explored in antiphospholipid syndrome (APS); therefore, we compared HRQoL between APS patients and the general population and assessed the impact of thromboembolic history.

Methods: HRQoL was measured in a multicentre cohort study by the Medical Outcomes Study Short-Form 36 (MOS-SF-36) questionnaire. HRQoL scores were compared to the French general population norms.