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Background: Understanding the mechanism by which viruses enter their target cell is an essential part of understanding their infectious cycle. Previous studies have focussed on the multiplicity of viral envelope proteins that need to bind to their cognate receptor to initiate entry. Avian sarcoma and leukosis virus Envelope protein (ASLV Env) mediates entry via a receptor, Tva, which can be attached to the cell surface either by a phospholipid anchor (Tva800) or a transmembrane domain (Tva950). In these studies, we have now investigated the number of target receptors necessary for entry of ASLV Env-pseudotyped virions., Results: Using titration and modelling experiments we provide evidence that binding of more than one receptor, probably two, is needed for entry of virions via Tva800. However, binding of just one Tva950 receptor is sufficient for successful entry., Conclusions: The different modes of attachment of Tva800 and Tva950 to the cell membrane have important implications for the utilisation of these proteins as receptors for viral binding and/or uptake.

Background: A problem likely to be encountered in any cancer immunotherapy based on vaccination with a single protein or peptide is variation in the host response. A particularly informative example is provided by the two oncogenic proteins, one intracellular and the other extracellular, encoded by the avian erythroblastosis virus (AEV), homologs of the thyroid hormones receptor (THsR) and the epithelial growth factor receptor (EGFR), respectively., Materials and Methods: Antibodies to these two proteins were assayed by radioimmune precipitation (RIP) in sera from MHC-congenic rats immunized by virally induced tumors., Results: Among the four haplotypes tested, RT1(1) rats exhibited a significantly lower response to the EGFR homolog than the high responders RT1c and RT1u, while RT1a rat strains had an intermediate response. Analysis of the recombinant haplotype RT1ac indicated that the response is controlled, as expected, by the class II locus of the MHC. In contrast, these rat strains responded uniformly to the intracellular THsR homolog., Conclusions: These results support the hypothesis that MHC restriction of the response to self-related proteins reflects mainly a tolerance mechanism. They sound a note of warning for cancer vaccine development, and also one of positive advice. The likelihood of MHC restriction suggests that a widely applicable polyvalent vaccine should be the final aim in cancer immunotherapy. Yet, paradoxically, evidence of MHC restriction can help establish that a candidate vaccine is likely to prove effective.