FUNCTIONAL DOMAINS IN THE RETROVIRAL TRANSMEMBRANE PROTEIN

The envelope glycoproteins of the mammalian type C retroviruses consis t of two subunits, a surface (SU) protein and a transmembrane (TM) pro tein. SU binds to the viral receptor and is thought to trigger conform ational changes in the associated TM protein that ultimately lead to t he fusion of viral and host cell membranes. For Moloney murine leukemi a virus (MoMuLV), the envelope protein probably exists as a trimer, We have previously demonstrated that the coexpression of envelope protei ns 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 ab ilities of a panel of fusion-defective TM mutants to complement each o ther. 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 ac ids of the MoMuLV TM (the R peptide) are cleaved by the viral protease , resulting in an increased fusogenicity of the envelope protein, We h ave 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 sug gest that R peptide cleavage enhances the fusogenicity of the envelope protein by influencing the interaction of two distinct regions in the TM ectodomain.