|HEAD||Prof. WAIN-HOBSON Simon / firstname.lastname@example.org|
|MEMBERS||Dr CERVANTES GONZALEZ Minerva / Dr CHENCINER Nicole / Dr GUÉTARD Denise
Dr LANGLADE-DEMOYEN Pierre / MICHEL Marie / PETIT Vincent
PUYRAIMOND-ZEMMOUR David / RENARD Myrtille / Dr SALA Monica
Dr VARTANIAN Jean-Pierre
Research is focused around three areas all of which touch questions of HIV biology. The first seeks to explore the impact of HIV-1 promoter polymorphisms on viral replication in vivo. To realize this, SHIV promoter chimeras have already shown that the HIV-1 clade C promoter is particularly well adapted to replication in the gut and can out-compete clade B and E viruses in vivo. These studies are being expanded to clade A and F chimeras because of their predominance in the HIV-1 pandemic (clade A) and recent spread in South America on a clade B background (clade F).
A second axe concerns HIV vaccination. By simple substitution of the SIV promoter by that of the widely used immediate early cytomegalovirus promoter we developed the most strongly attenuated SIV strain to date capable of containing a challenge virus by three orders of magnitude. Nothing comparable exists. Present research is designed to generate a non-integrating derivative. On another tack, we have optimized class I HIV-1 polyepitopes and, in collaboration with plant biotechnologists, we have generated transgenic plants capable of expressing multiple class I polyepitopes in particulate form. The efficiency of induction of cellular immune response at the mucosal and systemic levels in double transgenic HLA-A2.1-HLA-DR1 mice is currently being assessed.
The third line of work concerns the genetic editing of retroviruses and RNA viruses by host cell deaminases. Members of the APOBEC3 family of enzymes can decimate the HIV genome in the absence of a functional Vif gene product. We developed a simple and highly PCR based method to selectively amplify such genomes. It was possible to show that a variety of retroviruses are vulnerable to genetic editing by these deaminases albeit to a lesser extent than HIV. We showed that APOBEC3G was induced in the liver by interferon-α in vivo. From this we moved on to study adenosine deamination of RNA viral genomes by another interferon-α induced enzyme, ADAR-1L. From this starting point, over the next few years we would like to understand the molecular basis of the attenuation of a number of RNA virus vaccines such as measles, mumps and rubella.
|Publications 2006 of the unit on Pasteur's references database|
Activity Reports 2006 - Institut Pasteur
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