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Ce document constitue le rapport final de la prospective "les protéines animales et végétales : de la production aux marchés et à la consommation" engagée par l'INRA depuis 1997. Cette prospective a pour objectif d'éclairer les principaux acteurs de la recherche, et en particulier l'INRA, en élaborant différents scénarios envisageables pour l'avenir et en proposant des stratégies de recherche adaptées à chacun de ces scénarios. Ce rapport final comporte trois grandes parties : l'élaboration d'une situation d'état du système des protéines et l'identification des processus, de sa dynamique actuelle, puis la construction de scénarios d'évolution à partir d'hypothèses, et enfin, l'analyse des conséquences en termes de stratégies de recherche.

Ce document constitue le rapport final de la prospective "les protéines animales et végétales : de la production aux marchés et à la consommation" engagée par l'INRA depuis 1997. Cette prospective a pour objectif d'éclairer les principaux acteurs de la recherche, et en particulier l'INRA, en élaborant différents scénarios envisageables pour l'avenir et en proposant des stratégies de recherche adaptées à chacun de ces scénarios. Ce rapport final comporte trois grandes parties : l'élaboration d'une situation d'état du système des protéines et l'identification des processus, de sa dynamique actuelle, puis la construction de scénarios d'évolution à partir d'hypothèses, et enfin, l'analyse des conséquences en termes de stratégies de recherche.

International audience; The viability of rat embryo cells immortalized by thermosensitive mutants of SV40 or polyoma Large T antigen is impaired at the non-permissive temperature thus demonstrating that the immortal phenotype is dominantly maintained by Large T antigens. We have observed that exposing these cells to the restrictive temperature not only induces growth arrest but also causes apoptotic cell death. We present evidence supporting the model that polyomaviruses may indeed establish immortality by antagonizing the lethal effects of tumor suppressor genes via physical interactions between their products and Large T antigens. In the case of SV40-immortalized cells REtsAF, shift-up to 39.5 degrees C dissociates Large T antigen/p53 complexes releasing wild-type p53 molecules capable of inducing apoptotic cell death. In polyomavirus-immortalized cells, apoptosis may result from an alternative pathway mediated by other unidentified negatively acting molecules.

Three strains of mice (Swiss albinos, C57BL/6,C3H/OuJ) were injected intravenously with 3.7 x 10(6) colony forming units (CFU) of M. tuberculosis, H37RV, sensitive and resistant to antibiotics (90% of bacilli sensitive, 9% resistant to Streptomycin and 0.9% resistant to Kanamycin). Two weeks later, chemotherapy was started 6 days a week for a 6-month period with isoniazid (INH) and rifampicin (RMP). Twenty mice of each strain were killed at the end of the chemotherapy and the others were kept without antibiotics for a second 6-month follow-up period before being killed. The early multiplication of bacilli during the first 2 weeks following infection and before chemotherapy, was similar in the three strains of mice. Chemotherapy had the same apparent efficacy in the three strains of mice, nearly all the mice being cured as assessed by a negative spleen culture on Loewenstein-Jensen medium at the end of chemotherapy. But after the 6-month follow-up period, the C3H strain presented a statistically significantly higher level of positive spleen culture ('relapse') than seen in the C57BL/6 strain, and an increased number of mycobacteria per relapsing mouse spleen. It has been estimated with the help of resistant and sensitive bacilli that the relapses were due in most of the cases to the regrowth of one or very few bacilli, giving a clone. It seems that the C3H strain of mice, known to carry the Bcg-r allele of the Bcg gene, might be less able to develop a specific acquired resistance capable of stopping the delayed development of a highly virulent strain of mycobacteria.

The resistance to Mycobacterium bovis (BCG) of lines of mice selected for high (H) or low (L) antibody responsiveness was estimated from the rate of BCG multiplication in the organs. During the first 2 weeks after i.v. infection with 5 X 10(6) CFU, BCG multiplied faster in the spleens of H than of L mice. Afterwards there was a more drastic reduction of viable BCG counts in H mice than in L mice so that the residual BCG counts were significantly lower in H mice than in L mice, not only in the spleen but also in the liver and lungs. On the 14th day of infection, the spleen and liver enlargement and the increase of phagocytic activity were similar in the two lines, suggesting an identical T lymphokine release. In contrast with BCG, during the first 2 weeks after infection with 7 X 10(5) CFU, M. tuberculosis (H37Rv) multiplied in the spleens of L mice at a similar or a slightly faster rate than in the spleens of H mice. On the 4th week, the viable H37Rv counts were reduced in H mice whereas L mice did not survive the infection. In mice vaccinated with BCG 5 months before virulent challenge, the multiplication of H37Rv was inhibited in the H and L lines. The protective effect of BCG is therefore stronger in L mice taking into account their higher innate susceptibility to H37Rv. This might be due to the higher level of living BCG found in L mice at the time of challenge.

Chimpanzees are one of the few species, along with humans, susceptible to persistent HIV-1 infection. However, HIV-infected chimpanzees do not exhibit the marked immune system alterations seen in humans and remain relatively resistant to AIDS. In humans, HIV infection leads to unresponsiveness of T cells in response to TCR stimulation, associated with increased T cell death by apoptosis. In an effort to understand some of the mechanisms used to limit lentivirus infection in African nonhuman primates, we compared apoptosis in infected humans vs chimpanzees in CD4 and CD8 T cells in relation with the expression of Bcl-2 and Fas molecules. The intensity of apoptosis in CD4 and CD8 T cells from infected chimpanzees was very low, was not inducible by several TCR-dependent activators, and was comparable to that detected in noninfected chimpanzees. Moreover, CD45RO+ and HLA-DR+ subsets, which were shown to exhibit ex vivo a high propensity to undergo apoptosis in infected humans, were not modified in infected chimpanzees. Interestingly, in contrast to the situation found in infected humans, Fas ligation by agonistic Abs or recombinant human Fas ligand on CD4 and CD8 T cells from infected chimpanzees did not induce apoptosis in these subsets even when Bcl-2 was down-regulated. Finally, this resistance to apoptosis was associated with the predominance of CD3 T cells with a Th1 phenotype. Together these observations argue for a strong relationship among the absence of chronic immune stimulation in HIV-1-infected chimpanzees, the normal control of lymphocyte survival, and the resistance to disease progression.

High titres of pertussis toxin (PT) antibody have been shown to be predictive of recent infection with Bordetella pertussis. The seroprevalence of standardized anti-PT antibody was determined in six Western European countries between 1994 and 1998 and related to historical surveillance and vaccine programme data. Standardized anti-PT titres were calculated for a series of whole-cell and acellular pertussis vaccine trials. For the serological surveys, high-titre sera (>125 units/ml) were distributed throughout all age groups in both high- (>90%) and low-coverage (

HIV infection is marked by the progressive destruction of the CD4 T lymphocyte subset, an essential component of the immune system and a vital source of cytokines required for differentiation of natural killer (NK) and gamma delta T cells, for maturation of B lymphocytes into plasmocytes, and for differentiation of CD8+ T cells into virus-specific cytotoxic T lymphocytes. CD4 T lymphocytes are also a source of chemokines which control migration of lymphocytes to the site of infection and which also inhibit HIV entry into CD4-expressing targets. Continuous production of viral proteins leads to an unbalanced immune activation and to the triggering of apoptotic programs, turning mononuclear cells, including CD4 T cells, CD8 T cells and APC, into effectors of apoptosis, leading to fratricidal destruction of healthy uninfected cells expressing the death receptors. Inappropriate PCD is also responsible for the disappearance of T helper cells primed for type-1 cytokine synthesis, thus contributing to the lack of survival factors which could prevent spontaneous lymphocyte apoptosis. Under potent anti-retroviral therapies, a significant decrease in spontaneous, TCR- and CD95-induced lymphocyte apoptosis is observed, concomitant with a partial quantitative and qualitative restoration of the immune system in treated patients. However, owing to the suppressive effect of anti-retroviral drugs on physiological apoptosis, these therapies are associated with alteration of TNF-alpha-regulated T cell homeostasis, leading to an accumulation in the blood of T cells primed for TNF-alpha synthesis, and contributing to the development of a new syndrome associated with these treatments, the lipodystrophy syndrome.