Mécanismes physiopathologiques de l’infection du système nerveux central par les flavivirus

International audienceFlaviviruses are important human pathogens. Transmitted by the bite of infected mosquitoes, Flaviviruses such as West Nile and Japanese encephalitis may reach the central nervous system where they can elicit severe diseases. Their ability to cross the blood-brain-barrier is still poorly understood. The newly emerging Zika Flavivirus on the other hand very rarely reaches the brain of adults, but can infect neural progenitors in the developing central nervous system of fetuses, eliciting devastating congenital malformations including microcephaly. This short review focuses on selected aspects of West Nile, Japanese encephalitis and Zika virus pathophysiological features such as neuroinvasion and neurovirulence, and highlights what we know about some possible mechanisms involved in Flaviviral neuropathogenesis.Les Flavivirus sont d’importants pathogènes humains. Transmis par la piqûre de moustiques infectés, les flavivirus tels le virus West Nile et de l’encéphalite japonaise sont capables d’atteindre le système nerveux central au sein duquel ils peuvent provoquer des maladies graves. Leur capacité à traverser la barrière hématoencéphalique est encore mal comprise. En revanche, le nouveau flavivirus émergent Zika accède rarement le cerveau des personnes adultes, alors qu’il est capable d’infecter les progéniteurs neuronaux dans le système nerveux central en développement du fœtus, où il suscite de terribles malformations congénitales incluant la microcéphalie. Cette courte revue est centrée sur quelques aspects de la physiopathologie des virus West Nile, de l’encéphalite japonaise et Zika tels la neuroinvasion et la neurovirulence, et met en lumière ce que nous savons de quelques mécanismes possibles mis en jeu lors de la neuropathogenèse induite par ces virus

Identifying Attenuating Mutations: Tools for a New Vaccine Design against Flaviviruses

International audienceEmerging Flaviviruses pose an increasing threat to global human health. To date, human vaccines against yellow fever virus (YFV), Japanese encephalitis virus (JEV), dengue virus (DV), and tick-borne encephalitis virus (TBEV) exist. However, there is no human vaccine against other Flaviviruses such as Zika virus (ZIKV) and West Nile virus (WNV). In order to restrict their spread and to protect populations against the diseases they induce, vaccines against these emerging viruses must be designed. Obtaining new live attenuated Flavivirus vaccines using molecular biology methods is now possible. Molecular infectious clones of the parental viruses are relatively easy to generate. Key mutations present in live attenuated vaccines or mutations known to have a key role in the Flavivirus life cycle and/or interactions with their hosts can be identified by sequencing, and are then inserted in infectious clones by site-directed mutagenesis. More recently, the use of chimeric viruses and large-scale reencoding and introduction of microRNA target sequences have also been tested. Indeed, a combination of these methods will help in designing new generations of vaccines against emerging and reemerging Flaviviruses

New millenium. The need for new vaccines.

International audienceIntroduction: Although vaccination has led to the control of major diseases during the past 200 years, new (HIV, hepatitis C) and old (tuberculosis, malaria, acute respiratory infections, etc.) diseases alike killed 17 million people in 1997. However, the lives of three million children are saved each year owing to the WHO expanded programme of immunization (EPI), proving, if necessary, that vaccination is an effective tool for disease prevention and control. Unfortunately, it is also clear that vaccination does not reach the populations that most need it

Etude de l'interaction entre la protéine de membrane des flavivirus et la chaîne légère de dynéineTcex-1

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Report on the International Symposium on Vaccinology, November 18-20, Paris, France, organized by the Académie des Sciences and the Marcel Mérieux Foundation.

International audienc

A LIVE AND ATTENUATED FLAVIVIRUS COMPRISING A MUTATED M PROTEIN FIELD OF THE INVENTION 5 BACKGROUND OF THE INVENTION

The application relates to the attenuation of flaviviruses, such as West Nile Virus (WNV). The application notably provides a live and attenuated flavivirus, such as a WNV, comprising a mutated M protein. Said mutated M protein comprises or consists of a sequence, wherein the amino acids at position 36 in the ectodomain and position 43 in the transmembrane 10 domain 1 in said sequence are mutated. The application also provides additional embodiments deriving from said live and attenuated flavivirus, such as a WNV, such as nucleic acids, cDNA clones, immunogenic compositions as well as uses and methods

Nucleotide sequence of the M segment of Germiston virus: comparison of the M gene product of several bunyaviruses.

International audienceThe complete nucleotide sequence of the M RNA segment of Germiston bunyavirus was determined from plasmids containing overlapping M cDNA inserts. The M segment is 4534 nucleotides long and contains a 50-base-long inverted terminal repeat which can form a stable hydrogen-bonded secondary structure with a delta G of -45.8 kcal/mol. The RNA molecule complementary to viral RNA contains a single large open reading frame that encodes a 1437 amino acid-long protein with hydrophobic amino and carboxy terminal regions, which could represent signal and anchor sequences, respectively. It is presumed that this gene product is the polyprotein precursor to glycoproteins G1 and G2 and to the nonstructural polypeptide NSM. The nucleotide and amino acid sequences of the M RNA of Bunyamwera virus (prototype of the serogroup) and snowshow hare and La Crosse viruses (California serogroup) (Lees et al., 1986; Eshita and Bishop, 1984; Grady et al., 1987) were compared to those of Germiston virus. An overall amino acid sequence homology of 44% was found between Germiston and snowshoe hare viruses and of 61% between Germiston and Bunyamwera viruses. Most of the cysteines, three out of seven of the potential glycosylation sites, as well as the N and C terminal hydrophobic domains, are conserved between the four viruses

The TL MHC class Ib molecule has only marginal effects on the activation, survival and trafficking of mouse small intestinal intraepithelial lymphocytes

International audienceThymus leukemia antigen (TL) is an MHC class Ib molecule that is highly conserved in rats and mice with no obvious human homolog. TL is expressed in mouse small intestinal epithelial cells and is known to interact with CD8alphaalpha homodimers, which are expressed by intraepithelial lymphocytes (IELs), some other T cell subsets and some non-T cells such as a subset of dendritic cells. We show here that TL is abundantly expressed on the basolateral surface of mouse small intestinal epithelial cells and that expression is abrogated in beta2m-/- mice but unaffected in TCR-/- mice or CD8alpha chain-/- mice. We demonstrate that the interaction between TL and CD8alphaalpha is not necessary for IEL survival in vitro or in vivo and does not modulate IEL trafficking in vivo. TL co-stimulation of alpha-CD3 antibody-activated IELs resulted in modestly enhanced production of IFN-gamma in one subset of IELs. The lack of effect on IEL survival and trafficking and the modest effect on IFN-gamma production suggest that the functional consequences of TL interaction with CD8alphaalpha as well as the more general biological role of TL in mucosal immunity remains to be discovered