THE YXXL SIGNALING MOTIFS OF THE BOVINE LEUKEMIA-VIRUS TRANSMEMBRANE PROTEIN ARE REQUIRED FOR IN-VIVO INFECTION AND MAINTENANCE OF HIGH VIRAL LOADS

The bovine leukemia virus (BLV) transmembrane protein (gp30) contains three YXXL motifs at its carboxyterminal end. Two of these motifs have been implicated in vitro in signal transduction pathways from the ext ernal to the intracellular compartment. In order to analyze the biolog ical relevance of these motifs in vivo, recombinant BLV proviruses wer e constructed. A mutation of the tyrosine residue of the second YXXL m otif completely destroyed the infectious potential of the virus in she ep, In contrast, the tyrosine of the first motif appeared to be dispen sable for infectivity. However, the propagation of the recombinant vir us within the animal was greatly impaired (as demonstrated by PCR and enzyme-linked immunosorbent assay). These recombinant BLVs thus exhibi t an attenuated phenotype. Altogether, our data demonstrate the import ance of the YXXL motifs of the BLV transmembrane protein for in vivo i nfection and viral propagation.