Inserm U332, Institut Cochin de génétique moléculaire, 22, rue Méchain, 75014 Paris
- Key words: HTLV-I - Envelope glycoproteins - Retrovirus.
- Page(s) : 463-9
- Published in: 1997
HTLV-I is a pathogenic human retrovirus, which, as a unique feature, is transmitted almost exclusively via cell-to-cell contact and not via cell-free particles. The envelope glycoproteins play a crucial role in the infection process, and their study should thus contribute to an understanding of the molecular bases underlying the singular mode of HTLV-I transmission. The HTLV-I glycoproteins, like those of the other retroviruses, are initially synthesized as a precursor, which is subsequently cleaved into two mature products expressed at the cell surface : the SU protein, responsible for receptor recognition, and the TM protein, which drives the fusion process. The intracellular maturation of the HTLV-I glycoproteins is tightly controlled, and any modification of their structure, which is probably very compact, results in a loss of function. Two domains in the SU protein, which have been defined by mutagenesis studies as critical for envelope functions, and to which epitopes recognized by neutralizing antibodies have been mapped, are likely to be involved in the binding of HTLV-I to its as yet undefined receptor. The leucine zipper-like motif of the TM protein is crucial for viral function and, in this respect, HTLV-I behavior conforms to that of the other enveloped viruses. Noteworthy, in contrast, is the involvement of the TM ectodomain in post-fusion events required for viral entry into a new target cell ; this perhaps represents a unique feature of HTLV-I transmission. Further searches for distinctive properties should prove valuable, since the current data suggest that HTLV-I infectivity is limited by the accumulation of functional deficiencies in both the envelope glycoproteins and the core proteins. Finally, studies on the HTLV-I envelope glycoproteins should help in the design of a vaccine, the feasibility of which is favored by the remarkable genetic conservation of this retrovirus.