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J Virol, April 1998, p. 3432-3435, Vol. 72, No. 4
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Evidence for Cooperation between Murine Leukemia Virus Env Molecules in Mixed Oligomers

Alan Rein,1,* Chinglai Yang,2 Jacqueline A. Haynes,1,dagger Jane Mirro,1 and Richard W. Compans2

Retroviral Genetics Section, ABL Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702,1 and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 303222

Received 19 August 1997/Accepted 12 December 1997

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.


* Corresponding author. Mailing address: Retroviral Genetics Section, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, P.O. Box B, Bldg. 535, Rm. 211, Frederick, MD 21702. Phone: (301) 846-1361. Fax: (301) 846-7146. E-mail: rein{at}ncifcrf.gov.

dagger Present address: Vaccine Bioprocessing Research and Development, Merck and Company, West Point, PA 19486.




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