Evidence for cooperation between murine leukemia virus Env molecules in mixed oligomers.
A retroviral Env molecule consists of a surface glycoprotein (SU) complexed 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 polymorphic, with SU proteins of different viral isolates directed towards different cell surface receptors. During maturation of the released virus particle, the 16 C-terminal residues of TM (the R peptide or p2E) are removed from the protein by the viral protease; this cleavage is believed to activate the membrane-fusing potential of MuLV Env. We have tested the possibility that different MuLV Env proteins in the same cell can interact with each other, both physically and functionally, in mixed oligomers. We found that coexpressed Env molecules can be precipitated 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 fusion 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 respect to the mechanism of induction of membrane fusion, for the genetic analysis of Env function, and for the design of targeted retroviral vectors for gene therapy.
Rein
A
A
Retroviral Genetics Section, ABL Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702, USA. rein@ncifcrf.gov
Yang
C
C
Haynes
J A
JA
Mirro
J
J
Compans
R W
RW
D016475:3T3 Cells; D000818:Animals; D002459:Cell Fusion; D002461:Cell Line, Transformed; D017353:Gene Deletion; D015686:Gene Products, env / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008979:Moloney murine leukemia virus / Q000235:genetics / Q000378:metabolism*; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics / Q000378:metabolism*; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*
D015686:Gene Products, env; D015682:Retroviridae Proteins, Oncogenic; D014763:Viral Matrix Proteins; C085823:murine leukemia virus protein p2E