Our primary interest is the pathogenesis of HIV and SIV infection. It is a truism to say that the raison d'être of the immune system is to control and eliminate foreign microbes and antigens. This means that T cells are activated by the presence of antigen. In the case of HIV/SIV these cells are prey to the virus. Defining in vivo the temporal and spatial events in this process is our preoccupation.

PART 1

The primary interest of the unit is the pathogenesis of HIV and SIV infection. Just how does the virus destroy the immune system ? Given that the raison d'être of the immune system is to clear antigen via the activation of specific T cells, antigen actually drives virus replication as HIV/SIV preys on activated helper T cells. Using the SIV macaque model the unit has been concentrating on describing this process within infected germinal centres and other sites of inflammatory responses. T cell activation by antigen results in transcriptional activation of latent SIV proviruses and subsequent viral production. The production of virus in turns recruits specific killer lymphocytes to the site. What has become apparent is the relative dynamics of this process : there is a small window of <24 hours during which virus is made. Thereafter the site is sterilised by the killer lymphocytes. As the virus is one step ahead, it effectively escapes the immune system. Depending on the animal the window can be much shorter : these cases correlate with slow progression.


PART 2

A second research axis involves the production of SIV chimeras with exchanged promoters. One SIV construct involving a constitutively expressed promoter shows very low viral load despite a full complement of viral proteins. This indicates that the level of virus replication in relation to immune responses is what counts and that the SIV/HIV proteins are not per se endowed with properties which ensure escape. The modification of viral tropism is being pursued.

Michèle Chahine, Institut Pasteur : mchahine@pasteur.fr

Nicole Chenciner, Chargée de Recherche, Institut Pasteur: nchencin@pasteur.fr

Peter Sommer, Post-Doc, Boursier CEE : psommer@pasteur.fr

Michel Henry, Technicien Supérieur, Institut Pasteur : michael@pasteur.fr