The avian retrovirus E26 is unique among acute leukemia viruses in its ability to induce transformation of cells belonging to either the myeloid or erythroid lineage.
Using an antiserum to a bacterially expressed polypeptide corresponding to 56 amino acids of v‐ets, we previously identified in chicken tissues a protein of 54 kd (p54c‐ets) which shares extensive sequence homology to the v‐ets‐encoded domain of the E26‐transforming protein p135gag‐myb‐ets and is thus apparently encoded by the c‐ets proto‐oncogene. We report here that the anti‐ets serum specifically identifies in chicken cells a second set of proteins of 60 kd (p60), 62 kd (p62) and 64 kd (p64) which appear to be highly related to each other but display only a limited domain of homology with p54c‐ets and p135gag‐myb‐ets and are thus probably encoded by a gene(s) partially related to, but different from c‐ets. In contrast to p54c‐ets which is expressed at high levels in chicken lymphoid tissues, prominent syntheses of p62 and p64 were found in both normal and transformed chicken macrophages but not in avian cells corresponding to immature stages of the myeloid differentiation pathway. These observations together with the fact that differentiation of avian myeloblastosis virus‐transformed myeloblasts into macrophage‐like cells after treatment with 12‐O‐tetradecanoylphorbol‐13‐acetate is accompanied by the synthesis of p62 and p64 suggest a role for these proteins in chicken macrophage differentiation or function. Induction of differentiation of human leukemia cell lines HL60 and U937 into macrophages is also accompanied by the increased synthesis of c‐ets‐encoded 68 kd, 62 kd and 58 kd proteins.
The identification in the UK of 4 v-CJD infected patients thought to be due to the use of transfused Red Blood Cell units prepared from blood of donors incubating v-CJD raised major concerns in transfusion medicine. The demonstration of leucocyte associated infectivity using various animal models of TSE infection led to the implementation of systematic leuco-depletion (LD) of Red Blood cells concentrates (RBCs) in a number of countries. In the same models, plasma also demonstrated a significant level of infectivity which raised questions on the impact of LD on the v-CJD transmission risk. The recent development of filters combining LD and the capture of non-leucocyte associated prion infectivity meant a comparison of the benefits of LD alone versus LD/prion-reduction filters (LD/PR) on blood-borne TSE transmission could be made. Due to the similarity of blood/plasma volumes to human transfusion medicine an experimental TSE sheep model was used to characterize the abilities of whole blood, RBCs, plasma and buffy-coat to transmit the disease through the transfusion route. The impact of a standard RBCs LD filter and of two different RBCs LD/PR prototype filters on the disease transmission was then measured. Homologous recipients transfused with whole-blood, buffy-coat and RBCs developed the disease with 100% efficiency. Conversely, plasma, when intravenously administered resulted in an inconstant infection of the recipients and no disease transmission was observed in sheep that received cryo-precipitated fraction or supernatant obtained from infectious plasma. Despite their high efficacy, LD and LD/PR filtration of the Red Blood Cells concentrate did not provide absolute protection from infection. These results support the view that leuco-depletion strongly mitigates the v-CJD blood borne transmission risk and provide information about the relative benefits of prion reduction filters.
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