Analysis of functional conservation in the surface and transmembrane glycoprotein subunits of human T-cell leukemia virus type 1 (HTLV-1) and HTLV-2.
Human T-cell leukemia virus types 1 and 2 (HTLV-1 and HTLV-2) are closely related retroviruses with nucleotide sequences that are 65% identical. To determine whether their envelope glycoproteins function similarly and to define the molecular determinants of HTLV-2 envelope-mediated functions, we have used pseudotyped viruses and have introduced mutations into regions of the HTLV-2 glycoproteins homologous to those known to be important for HTLV-1 glycoprotein functions. The envelopes of the two viruses could be exchanged with no loss of infectivity, suggesting that the glycoproteins function in broadly similar ways. However, comparative analysis of the HTLV-1 and HTLV-2 glycoproteins showed subtle differences in the structure-function relationships of the two surface glycoprotein (SU) subunits, even though they recognize the same receptor. Indeed, mutations introduced at equivalent positions in the two SU glycoproteins resulted in different phenotypes in the two viruses. The scenario is the opposite for the transmembrane glycoprotein (TM) subunits, in which the functional domains of the two viruses are strictly conserved, confirming the involvement of the TM ectodomain in postfusion events required for full infectivity of the HTLVs. Thus, although they recognize the same receptor, the HTLV-1 and HTLV-2 SU subunits have slightly different ways of transducing the conformational information that primes a common fusion mechanism effected by similar TM subunits.
INSERM U332, Institut Cochin de Génétique Moléculaire, 22 rue Méchain, 75014 Paris, France.
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D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D015686:Gene Products, env / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D006367:HeLa Cells; D015368:Human T-lymphotropic virus 1 / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D015367:Human T-lymphotropic virus 2 / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008561:Membrane Fusion; D008969:Molecular Sequence Data; D016296:Mutagenesis; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D054299:env Gene Products, Human Immunodeficiency Virus
D015686:Gene Products, env; D015682:Retroviridae Proteins, Oncogenic; D054299:env Gene Products, Human Immunodeficiency Virus; C055265:gp21 protein, Human T-lymphotropic virus 1; C055266:gp46 protein, Human T-cell leukemia virus type I; C069568:gp46 protein, Human immunodeficiency virus 2; C069569:human T-cell leukemia virus type-II protein gp21