EVIDENCE FOR COOPERATION BETWEEN MURINE LEUKEMIA-VIRUS ENV MOLECULES IN MIXED OLIGOMERS

A retroviral Env molecule consists of a surface glycoprotein (SU) comp lexed with a transmembrane protein (TM). In turn, these complexes are grouped into oligomers on the surfaces of the cell and of the virion. In the case of murine leukemia viruses (MuLVs), the SU moieties are po lymorphic, with SU proteins of different viral isolates directed towar ds different cell surface receptors. During maturation of the released virus particle, the 16 C-terminal residues of TM (the R peptide or p2 E) are removed from the protein by the viral protease; this cleavage i s believed to activate the membrane-fusing potential of MuLV Env. We h ave tested the possibility that different MuLV Env proteins in the sam e cell can interact with each other, both physically and functionally in mixed oligomers. We found that coexpressed Env molecules can be pre cipitated out of cell lysates by antiserum which reacts with only one of them. Furthermore, they can evidently cooperate with each other: if one Env species lacks the R peptide, then it can apparently induce fu sion if the SU protein of the other Env species encounters its cognate receptor on the surface of another cell. This functional interaction between different Env molecules has a number of implications with resp ect to the mechanism of induction of membrane fusion, for the genetic analysis of Env function, and for the design of targeted retroviral ve ctors for gene therapy.