Human T-cell leukemia virus type 1 receptor expression among syncytium-resistant cell lines revealed by a novel surface glycoprotein-immunoadhesin.
The envelope glycoproteins of human T-cell leukemia virus type 1 (HTLV-1) perform functions that are crucial for virus entry into cells. The surface glycoprotein (SU) is responsible for viral recognition of, and binding to, target cells through its interaction with an unknown cell surface receptor. To facilitate molecular analysis of the receptor-binding properties of SU and to characterize the cellular receptor employed by HTLV-1, we have expressed a recombinant SU fused to the Fc domain of human immunoglobulin G. Here, we demonstrate that this novel SU-immunoadhesin retains both the biochemical properties of Fc and the receptor-binding specificity of the HTLV-1 SU. We use this SU-immunoadhesin to demonstrate, by direct cell surface binding assays, that the receptor used by HTLV-1 has been conserved through vertebrate evolution. Moreover, using murine-human somatic cell hybrids we provide data that do not support the previously assigned location for the HTLV-1 receptor on human chromosome 17. Most importantly, we show that many cell lines that are resistant to HTLV-1 envelope-mediated infection and syncytium formation express functional receptors that are recognized by the HTLV-1 SU. Based on our results, we suggest that for some HTLV-1-resistant cell lines the block to viral entry occurs at a late post-receptor-binding step of the entry process. Our findings will be of value in developing new strategies to identify the cellular receptor used by HTLV-1.
Jassal
S R
SR
Biomedical Research Centre, Ninewells Hospital and Medical School, The University of Dundee, Dundee DD1 9SY, Scotland.
Pöhler
R G
RG
Brighty
D W
DW
D000818:Animals; D002417:Cattle; D002460:Cell Line; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D002874:Chromosome Mapping; D004285:Dogs; D004331:Drosophila melanogaster / Q000166:cytology; D015686:Gene Products, env / Q000378:metabolism; D015726:Giant Cells / Q000502:physiology*; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D015368:Human T-lymphotropic virus 1 / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000378:metabolism; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015682:Retroviridae Proteins, Oncogenic / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism
D015686:Gene Products, env; D006023:Glycoproteins; C080823:HTLV-I receptor; D007141:Immunoglobulin Fc Fragments; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins; D015682:Retroviridae Proteins, Oncogenic; D014759:Viral Envelope Proteins; C055266:gp46 protein, Human T-cell leukemia virus type I