Infection expérimentale de veaux par le virus respiratoire syncytial bovin : évaluation de la persistance virale

Le Virus Respiratoire Syncytial Bovin (VRSB) est une cause majeure de maladie respiratoire des jeunes bovins. La persistance du VRSB et du VRS humain à pu être démontrée in vitro sur différentes lignées cellulaires et in vivo sur des cobayes ou sur des sujets immunodéprimés. En revanche, la persistance du VRS in vivo chez son hôte naturel immunocompétent n'a jamais pu être mise en évidence. Elle a pourtant depuis longtemps été fortement suspectée à partir des données épidémiologiques. En outre, le VRS possède plusieurs caractéristiques communes avec des virus susceptibles de persister. Dans notre expérience, conduite sur 25 veaux immunocompétents, les ARN messager et génomique par RT-PCR, ainsi que les protéines F et G par immunohistochimie ont été détectés dans les noeuds lymphatiques pulmonaires jusqu'à 71 jours après inoculation. La persistance du VRSB semble localisée dans les lymphocytes B. Les expériences de cocultures suggèrent que le virus est toujours capable de se répliquer, même si le virus n'a pas pu être isolé ni l'effet cytopathogène retrouvé. C'est la première fois que la persistance d'un VRS est prouvée chez son hôte spécifique

Dominance of the CD4 + T helper cell response during acute resolving hepatitis A virus infection

CD4+ T cells play a dominant role in control of acute HAV infection in chimpanzees.Hepatitis A virus (HAV) infection typically resolves within 4–7 wk but symptomatic relapse occurs in up to 20% of cases. Immune mechanisms that terminate acute HAV infection, and prevent a relapse of virus replication and liver disease, are unknown. Here, patterns of T cell immunity, virus replication, and hepatocellular injury were studied in two HAV-infected chimpanzees. HAV-specific CD8+ T cells were either not detected in the blood or failed to display effector function until after viremia and hepatitis began to subside. The function of CD8+ T cells improved slowly as the cells acquired a memory phenotype but was largely restricted to production of IFN-γ. In contrast, CD4+ T cells produced multiple cytokines when viremia first declined. Moreover, only CD4+ T cells responded during a transient resurgence of fecal HAV shedding. This helper response then contracted slowly over several months as HAV genomes were eliminated from liver. The findings indicate a dominant role for CD4+ T cells in the termination of HAV infection and, possibly, surveillance of an intrahepatic reservoir of HAV genomes that decays slowly. Rapid contraction or failure to sustain such a CD4+ T cell response after resolution of symptoms could increase the risk of relapsing hepatitis A

Conception et évaluation de différentes approches vaccinales contre le coronavirus associé au syndrome respiratoire aigu sévère

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Heterologous viral RNA export elements improve expression of severe acute respiratory syndrome (SARS) coronavirus spike protein and protective efficacy of DNA vaccines against SARS.

International audienceThe SARS-CoV spike glycoprotein (S) is the main target of the protective immune response in humans and animal models of SARS. Here, we demonstrated that efficient expression of S from the wild-type spike gene in cultured cells required the use of improved plasmid vectors containing donor and acceptor splice sites, as well as heterologous viral RNA export elements, such as the CTE of Mazon-Pfizer monkey virus or the PRE of Woodchuck hepatitis virus (WPRE). The presence of both splice sites and WPRE markedly improved the immunogenicity of S-based DNA vaccines against SARS. Upon immunization of mice with low doses (2 microg) of naked DNA, only intron and WPRE-containing vectors could induce neutralizing anti-S antibodies and provide protection against challenge with SARS-CoV. Our observations are likely to be useful for the construction of plasmid and viral vectors designed for optimal expression of intronless genes derived from cytoplasmic RNA viruses

Dominance of the CD4+ T helper cell response during acute resolving hepatitis A virus infection

Hepatitis A virus (HAV) infection typically resolves within 4–7 wk but symptomatic relapse occurs in up to 20% of cases. Immune mechanisms that terminate acute HAV infection, and prevent a relapse of virus replication and liver disease, are unknown. Here, patterns of T cell immunity, virus replication, and hepatocellular injury were studied in two HAV-infected chimpanzees. HAV-specific CD8(+) T cells were either not detected in the blood or failed to display effector function until after viremia and hepatitis began to subside. The function of CD8(+) T cells improved slowly as the cells acquired a memory phenotype but was largely restricted to production of IFN-γ. In contrast, CD4(+) T cells produced multiple cytokines when viremia first declined. Moreover, only CD4(+) T cells responded during a transient resurgence of fecal HAV shedding. This helper response then contracted slowly over several months as HAV genomes were eliminated from liver. The findings indicate a dominant role for CD4(+) T cells in the termination of HAV infection and, possibly, surveillance of an intrahepatic reservoir of HAV genomes that decays slowly. Rapid contraction or failure to sustain such a CD4(+) T cell response after resolution of symptoms could increase the risk of relapsing hepatitis A