|Director : WAIN-HOBSON, Simon (email@example.com)|
Work is centred around the immunopathology of SIV infection. Projects aim to illustrate the role of antigenic stimulation, the dynamic of infiltration of CTLs into inflammatory sites, SIV latency and strain differences among HIV-1 subtypes. Novel attenuated SIV vaccines are being developed.
Use of the SIV genetic variability in the study of the in vivo immunopathology in vivo, and simulation in silico.
Céline RENOUX-ELBE and Rémi CHEYNIER
The present study tries to analyse the role played by the activation of the immune system on the dynamics of viral replication. To do that, rhesus macaques immunised with different antigens were infected with SIVmac251. At regular time points, booster injections were realised in order to favour the infection of CD4+ T cells responding to those antigens. Then, delayed hypersensibility tests were made to create antigen-specific inflammatory sites.
By comparing SIV quasispecies at these sites to those in peripheral blood during booster injections, it should allow to describe lineages of SIV within T cells specific for particular antigens. These resultst will permit to draw up a model of virus replication taking into account antigenic stimulation of the immune system.
Construction of SIV/HIV chimeras: phenotypic analysis of different HIV-1 promoters in vivo
Mireille CENTLIVRE and Monica SALA
The aim of this project is to analyse the influence of major HIV-1 subtypes polymorphism on viral transcription, replication, cellular tropism and pathogenesis. To develop this study in vivo, HIV/SIV chimeras (SHIVs) have been constructed where the SIV genome presents non-overlapping Nef and LTR elements (STR), and the enhancer/core portion either of the HIV-1 B or C or E subtypes promoters (SHIV-1 B, E and C) replaces the homologous SIV region. These chimeras allow the phenotypic analysis of subtype-specific enhancer/core promoter regions and the evaluation of the influence of the LTR negative regulatory element (NRE) on the establishment of HIV-1 latency and persistence. Chimeric promoter functionality has been tested ex vivo and the characterisation of chimeric viruses is in progress.
The infiltration kinetics of SIV-specific T cells drawn to sites of high antigenic stimulation determines local in vivo viral escape
Philippe BLANCOU, Nicole CHENCINER and Rémi CHEYNIER
The local dynamics of simian imunodeficiency virus (SIV) replication is studied in rhesus macaque following antigenic stimulation triggered by a delayed type hypersensitivity (DTH) reaction. Early viral mRNA synthesis coincided with the infiltration of antigen specific T cells drawn to DTH sites. When the infiltration of anti-SIV specific T cells was rapid compared to the kinetics of viral assembly, the sites were sterilized before the transition to late viral mRNA synthesis occurred. When their infiltration was slow, ephemeral foci of replication were identified suggesting a novel mechanism allowing SIV or HIV1 to escape from the immune system. More recent work is centred on generating novel line attenuated SIV vaccines.
Contribution of different cell compartments to persistence and pathogenesis of SIV in vivo
HIV/SIV infects multiple cell types, including CD4+ Th1/2 T lymphocytes, macrophages, dendritic cells, monocytes and microglia to name just a few. The primary determinant of cell tropism is the interaction of viral glycoproteins with cellular receptors. Once entered the target cell, the long terminal repeat (LTR) can further modulate cell tropism mediating gene expression and efficient replication. The aim of this study is to modify the cell tropism of SIV by changing the promoter sequences within the LTR. Insertion of tissue-specific regulatory promoter elements into the viral LTR will enable a defined and restricted viral replication within particular compartments independent of the capability of virus variants to use various cellular receptors. Thus, the contribution of each cellular compartment to viral persistence and AIDS pathogenesis can be revealed.
Chimpanzees as a reservoir for persistent viral infections
Michel HENRY and Jean-Pierre VARTANIAN
Chimpanzees, our closest relatives, are hosts to a number of viruses homologous to human pathogens. Usually analyses are made with a single virus in mind. Here a study of a number of DNA viruses and retroviruses was undertaken on samples from four dead wild chimpanzees. Surprisingly, those animals were infected by different viruses (TT virus, HBV, adenovirus type 5, STLV-1, a simian herpes virus close to HHV-8, associated with Kaposi sarcoma). Chimpanzees constitute a rich source of microbes. However, given the highly related cellular biochemistries of chimpanzees and humans, the transfer of infections, perhaps in both directions, is probably easy. We are looking for novel viruses in feaces and urine samples of wild animals. We will follow our ideas on: 1) retroviruses (lentiviruses, oncoviruses and spumaviruses); 2) enteroviruses; 3) hepadnaviruses and flaviruses including HCV.
Staff of the Unité de Rétrovirologie Moléculaire
|Publications of the unit on Pasteur's references database|
|Office staff||Researchers||Scientific trainees||Other personnel|
WAIN-HOBSON, Simon, Institut Pasteur, Professeur, firstname.lastname@example.org
CHAHINE, Michèle, Institut Pasteur, email@example.com
CHENCINER, Nicole, Institut Pasteur, PhD, firstname.lastname@example.org
CHEYNIER, Institut Pasteur, PhD (seconded to IRCM/Montrel, Canada), email@example.com
SALA-SCHAEFFER, Monica, Institut Pasteur, PhD, firstname.lastname@example.org
VARTANIAN, Jean-Pierre, Institut Pasteur, PhD, email@example.com
BLANCOU, Philippe, Post-Doc
CENTLIVRE, Mireille, graduate student
RENOUX, Céline, graduate student
SOMMER, Peter, PhD, Post-Doc