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J Virol, July 1998, p. 5392-5398, Vol. 72, No. 7
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Functional Domains in the Retroviral Transmembrane Protein

Yi Zhao, Lunjian Zhu, Chris A. Benedict, Dagang Chen, W. French Anderson, and Paula M. Cannon*

Gene Therapy Laboratories, Norris Cancer Center, University of Southern California School of Medicine, Los Angeles, California 90033

Received 8 December 1997/Accepted 21 March 1998

The envelope glycoproteins of the mammalian type C retroviruses consist of two subunits, a surface (SU) protein and a transmembrane (TM) protein. SU binds to the viral receptor and is thought to trigger conformational changes in the associated TM protein that ultimately lead to the fusion of viral and host cell membranes. For Moloney murine leukemia virus (MoMuLV), the envelope protein probably exists as a trimer. We have previously demonstrated that the coexpression of envelope proteins that are individually defective in either the SU or TM subunits can lead to functional complementation (Y. Zhao et al., J. Virol. 71:6967-6972, 1997). We have now extended these studies to investigate the abilities of a panel of fusion-defective TM mutants to complement each other. This analysis identified distinct complementation groups within TM, with implications for interactions between different regions of TM in the fusion process. In viral particles, the C-terminal 16 amino acids of the MoMuLV TM (the R peptide) are cleaved by the viral protease, resulting in an increased fusogenicity of the envelope protein. We have examined the consequences of R peptide cleavage for the different TM fusion mutants and have found that this enhancement of fusogenicity can only occur in cis to certain of the TM mutants. These results suggest that R peptide cleavage enhances the fusogenicity of the envelope protein by influencing the interaction of two distinct regions in the TM ectodomain.

* Corresponding author. Mailing address: Norris Cancer Center, Rm. 633, USC School of Medicine, 1441 Eastlake Ave., Los Angeles, CA 90033. Phone: (213) 764-0673. Fax: (213) 764-0097. E-mail: pcannon{at}hsc.usc.edu.

J Virol, July 1998, p. 5392-5398, Vol. 72, No. 7
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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