Retroviruses and comparative pathology

Retroviruses are RNAviruses that infect and can induce disease in humans and animals. Retroviral infections in small ruminants and horses share common features: when serology is available, infected animals can be seronegative; infected animals inconstantely develop disease; infection and disease can be experimentaly induced. Animal retroviruses are a cause of spontaneous diseases, transmissible among animals and model systems of human diseases.Les rétrovirus sont des virus à ARN qui infectent et sont susceptibles de rendre malade l'homme et l'animal. Les infections rétrovirales des petits ruminants et des équidés ont des caractéristiques communes: lorsqu'il existe un diagnostic sérologique, des animaux infectés peuvent être séronégatifs; les animaux infectés ne sont pas toujours malades; l'infection et la maladie peuvent être reproduits expérimentalement. Au total, les rétrovirus animaux, en particulier des petits ruminants et des équidés, sont une cause de maladies spontanées, transmissibles chez ces animaux et peuvent être utilisés comme modèle de plusieurs maladies humaines

Enhanced HIV immune responses elicited by an apoptotic single-cycle SHIV lentivector DNA vaccine

BackgroundHIV remains a major public health issue in spite of antiretroviral therapy (ART). An innovative vaccine that can induce long-lasting and effective immunity is required to curb the persistently high numbers of new infections worldwide.MethodsA novel DNA vaccine was generated using a Simian-Human Immunodeficiency Virus (SHIV) backbone with a Zambian T/F clade C envelope and under the control of the caprine arthritis encephalitis virus long terminal repeats (LTRs) for constitutive expression. Due to the deleted integrase, this DNA vaccine “CSH-DIN-T/F Z331” performs only a single replication cycle. To increase immunogenicity, the co-expression of apoptotic genes (BAX, BAK, or caspase 8) incorporated at the end of Pol was tested to promote the release of apoptotic bodies taken up by dendritic cells leading to cross-presentation of antigen. The three vaccines (CSH-DIN-T/F Z331-BAX, CSH-DIN-T/F Z331-BAK, and CSH-DIN-T/F Z331-Cas8) were tested in vitro for expression and in vivo in BALB/cJ mice for immunogenicity.ResultsTransduced HEK293 cells co-cultured with CEMx174 confirmed the single replication cycle of the DNA vaccine and the induction of apoptosis by CSH-DIN-T/F Z331-Cas8 based on Annexin V expression. BALB/cJ mice were immunized with a combined intramuscular + intradermal/electroporation approach. Intracellular cytokine staining (ICS) from splenocytes collected 12 weeks post-prime/6 weeks post-boost demonstrated a clear superiority of caspase 8 expressing construct over the others, with higher proportions of IFN-γ-, IL-2-, and IL-21-producing CD8 T cells specific to Env, Gag, and Nef. The kinetics of immune response after various immunization schedules were also investigated.ConclusionThis novel single-cycle DNA vaccine with apoptotic genes demonstrated an enhanced immunogenicity primarily for antigen-specific CD8+ T-cell responses

Ongoing work on CAEV project in the veterinary school of Lyon group.

International audienc

Etude des risques de diffusion du virus de l’arthrite-encephalite caprine (CAEV) lors de l’application des protocoles de production d’embryons in vitro et du transfert embryonnaire

International audienc