Implication of the bovine leukemia virus transmembrane envelope protein in cell fusion and viral infectivity | Implication de la proteine transmembranaire d'enveloppe du virus de la leucemie bovine dans la fusion cellulaire et l'infectivite virale
1999
Gatot, J.S.
The bovine leukemia virus (BLV) is an excellent animal model to examine the mechanisms involved in viral-induced leukemia, in particular those linked to the human T-cell lymphotropic virus HTLV-1. The BLV transmembrane envelope protein (gp30) is implicated in a capital step of the virus replication cycle, the fusion with the target cell membrane, by insertion of its fusion peptide into the cellular membrane. By using a sensitive method of protein sequence analysis and by analogy with the Influenza A hemagglutinin structures, a model was established for the gp30 NH2-terminal portion. By this means, we have identified amino acids that seem to be crucial for the gp30 structural reorganisation leading to the projection of the fusion peptide. In order to estimate the implication of these residues for the BLV envelope structure and function, point mutations were introduced in the env gene of an infectious BLV molecular clone. Mutations were also introduced in the gp30 immunosuppressive region and in cytoplasmic motifs implicated in signal transduction in vitro. After expression of the mutated and wild-type envelope proteins in cell culture, the influence of the mutations on the envelope structural integrity and the fusogenic potential was evaluated. Finally, the infectious potential of the mutated proviruses was tested by direct injection into sheep. The comparison of in vitro and in vivo results shows notably that mutants unable to form syncytia in cell culture retain in vivo infectious potential and can even induce a proviral load close to the wild-type level in some animals. Our results underline the importance of experiments performed in an animal model in order to understand the molecular mechanisms specific to viro-induced leukemias.
اظهر المزيد [+] اقل [-]الكلمات المفتاحية الخاصة بالمكنز الزراعي (أجروفوك)
المعلومات البيبليوغرافية
تم تزويد هذا السجل من قبل University of Liège