Molecular mechanisms affecting HTLV type 1-dependent fusion at the cell membrane: Implications for inhibiting viral transmission

Infection with human T cell leukemia virus type 1 is detected by screening programs and contact follow-up procedures. Where chronic infection results in overt pathology, this is treated largely symptomatically and control of transmission relies on physical and educational constraints. The poor infec tious transmission rate of HTLV-1 has long been described but to date has n ot been exploited in preventative measures to combat the spread of the viru s. We undertook to investigate some of the molecular steps involved in HTLV -1 cell-cell fusion, the main mechanism of transmission. We showed that poo r transmission may relate in part to an inefficiency in adopting and mainta ining a fusion competent conformation of the HTLV-1 envelope TM protein, In cell-cell fusion, this deficiency can be complemented by accessory molecul es on both infected and target cells that stabilize the envelope/receptor i nteraction. In virion-cell fusion, this is less likely, leading to an ineff icient interaction and poor infectious transmission by cell-free virus. A d iscussion of the accessory molecules involved in HTLV-1 fusion is presented . This weak envelope-dependent interaction with target cells in the host ca n be potently disrupted by peptides that destabilize the TM protein structu re and significantly inhibit HTLV-1 fusion, These observations may be usefu l in the design of therapeutic agents to prevent HTLV-1 transmission.