INFLUENCE OF TRANSMEMBRANE DOMAINS ON THE FUSOGENIC ABILITIES OF HUMAN AND MURINE LEUKEMIA RETROVIRUS ENVELOPES

The envelopes of two highly divergent oncoviruses, human T-cell leukem ia virus type 1 (HTLV-1) and Friend murine leukemia virus (F-MuLV), ha ve distinct patterns of cellular receptor recognition, fusion, and syn cytium formation. To analyze the influence of the transmembrane envelo pe subunit (TM) on fusogenic properties, we substituted either the ent ire TM or distinct domains from F-MuLV for the corresponding domains i n the HTLV-1 envelope. Parental, chimeric, and truncated envelopes clo ned into a eukaryotic expression vector were monitored for fusogenic p otential in human, rat, and murine indicator cell lines by using a qua ntitative assay. This highly sensitive assay allowed us to assess the fusogenic properties and syncytium-forming abilities of the HTLV-1 env elope in murine NIH 3T3 cells. All chimeric envelopes containing extra cellular sequences of the F-MuLV TM were blocked in their maturation p rocess. Although deletions of the HTLV-1 cytoplasmic domain, alone and in combination with the membrane-spanning domain, did not prevent env elope cell surface expression, they impaired and suppressed fusogenic properties, respectively. In contrast, envelopes carrying substitution s of membrane-spanning and cytoplasmic domains were highly fusogenic. Our results indicate that these two domains in F-MuLV and HTLV-1 const itute structural entities with similar fusogenic properties. However, in the absence of a cytoplasmic domain, the F-MuLV membrane-spanning d omain appeared to confer weaker fusogenic properties than the HTLV-1 m embrane-spanning domain.