WW domains and retrovirus budding

It has long been known that retroviral Gag proteins, in groups of roughly 2000, can direct the budding of enveloped particles at the plasma membrane. We wish to report an observation that strongly suggests a role for host proteins in the final stages of virus release. One of the functional domains of Gag, the L domain, operates late in budding. The first L domain to be identified was that of HIV (human immunodeficiency virus). It is located near the carboxy terminus of Gag, in the p6 sequence, and its critical amino acids include P-T-A-P. In contrast, the L domain of Rous sarcoma virus (RSV) Gag is near the amino terminus in the p2b sequence and its critical residues are P-P-P-P-Y. The only other identified L domain is that of equine infectious anaemia virus (EIAV). L mutants of RSV can be restored to budding competence by attaching the L domain of HIV or EIAV to their carboxy termini. The Yes protein tyrosine kinase is located on the cytoplasmic face of the plasma membrane. It contains an SH3 domain, which permits interaction with Yap (Yes-associated protein) during signal transduction. Yap contains a "WW" motif--a sequence of 38 amino acids containing two widely spaced tryptophans. We tested the possibility that a WW domain might be involved in the RSV Gag late function.