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

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 infectious transmission rate of HTLV-1 has long been described but to date has not been exploited in preventative measures to combat the spread of the virus. We undertook to investigate some of the molecular steps involved in HTLV-1 cell-cell fusion, the main mechanism of transmission. We showed that poor transmission may relate in part to an inefficiency in adopting and maintaining a fusion competent conformation of the HTLV-1 envelope TM protein. In cell-cell fusion, this deficiency can be complemented by accessory molecules on both infected and target cells that stabilize the envelope/receptor interaction. In virion-cell fusion, this is less likely, leading to an inefficient interaction and poor infectious transmission by cell-free virus. A discussion of the accessory molecules involved in HTLV-1 fusion is presented. This weak envelope-dependent interaction with target cells in the host can be potently disrupted by peptides that destabilize the TM protein structure and significantly inhibit HTLV-1 fusion. These observations may be useful in the design of therapeutic agents to prevent HTLV-1 transmission.