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Little sequence information exists on the matrix-protein (MA) encoding region of small ruminant lentiviruses (SRLV). Fifty-two novel sequences were established and permitted a first phylogenetic analysis of this region of the SRLV genome. The variability of the MA encoding region is higher compared to the gag region encoding the capsid protein and surprisingly close to that reported for the env gene. In contrast to primate lentiviruses, the deduced amino acid sequences of the N- and C-terminal domains of MA are variable. This permitted to pinpoint a basic domain in the N-terminal domain that is conserved in all lentiviruses and likely to play an important functional role. Additionally, a seven amino acid insertion was detected in all MVV strains, which may be used to differentiate CAEV and MVV isolates. A molecular epidemiology analysis based on these sequences indicates that the Italian lentivirus strains are closely related to each other and to the CAEV-CO strain, a prototypic strain isolated three decades ago in the US. This suggests a common origin of the SRLV circulating in the monitored flocks, possibly related to the introduction of infected goats in a negative population. Finally, this study shows that the MA region is suitable for phylogenetic studies and may be applied to monitor SRLV eradication programs.

Effective therapy for prion diseases is currently unavailable. Recently, vaccination was shown to be effective in mouse models of a particular neurodegenerative conditions: Alzheimer's disease (AD). Here, we report that vaccination with synthetic oligopeptides homologous to the hamster (Mesocricetus auratus) prion protein augments survival time in animals infected intraperitoneally with 263K scrapie agent. For each hamster included in the study, prion-specific serum antibodies as well as deposition of pathological prion protein (PrPres), glial fibrillary acidic protein (GFAP), and mRNA expression for cytokines (TNF alpha, IL-1 beta, IL-10) in brain tissues were evaluated. In immunized animals, increased survival after challenge was associated with a reduction of cerebral lesion, PrP deposition and GFAP expression; in these animals, anti-prion protein peptide antibody levels were increased, and the expression of pro-inflammatory cytokines (TNF alpha and IL-1 beta) was reduced. Vaccination could be an effective therapeutic approach to postpone disease onset. (c) 2004 Elsevier Ltd. All rights reserved.

Immune defects, thyroid abnormalities, infections and coeliac disease are often associated with Down's syndrome (DS). However, the basis of the immune defects is still unclear in DS. In the present study, we show that peripheral CD4 T-cells were decreased in children with DS, while mean values of cytotoxic CD8 T-cells were comparable with those from healthy children. Circulating activated (CD3/HLA-DR positive) T-cells were increased and a large proportion of purified T-cells from DS were also positive for APO-I/FAS (CD95) antigen. To further explore the functional status of circulating activated T-cells, enriched CD3 lymphocytes were cultured for 3 h and were tested for positivity to annexin-V (ANX-V) and propidium iodide. T-cells with the early apoptotic phenotype were increased in cell cultures from DS children. Plasma levels of inteleukin-6 (IL-6) were higher in DS children than in healthy children. The incidence of coeliac disease was also increased in this group of children. Most DS children showed increased levels of circulating IgG or IgA specific for gliadin, and their plasma IL-6 levels correlated with those of antigliadin IgG. The number of CD4 circulating cells was very low in DS children with coeliac disease, was low in those with serum antigliadin antibodies and was normal in DS without antigliadin antibodies. An overload of dietary antigens and impaired nutrient absorption secondary to altered functioning of the gastrointestinal mucosa might interfere with normal immune responses by inducing programmed cell death in CD4 T-cells.