title: Human T lymphotropic virus I infection deregulates surface expression of the transferrin receptor.
abstract: Human T-lymphotropic virus I (HTLV-I) is an etiologic agent in adult T cell leukemia. In an effort to understand the relationship between HTLV-I infection and malignant transformation, we have examined transferrin receptor expression in HTLV-I-infected cells. Transferrin receptor expression in normal T cells is tightly regulated and essential for cell proliferation. We have used matched T cell sets originating from a normal donor, consisting of tetanus toxoid-specific normal T cell clones (TM3 and TM5) and their in vitro HTLV-I-infected counterparts (TM3H and TM5H). Using these matched sets of virus-infected and normal T cells, we have determined that HTLV-I infection leads to hyperexpression of surface transferrin receptors (five- to six-fold higher than normal counterparts). Although the growth rates of the virus-infected cells did not differ significantly from their normal controls, HTLV-I-infected cells constitutively hyperexpressed surface transferrin receptors, whereas the level of surface receptor expression of normal counterpart cells varied during the cycle of antigenic stimulation. Immunoprecipitation of total (surface plus cytoplasmic) transferrin expression showed that the HTLV-I-infected cells did not possess a greater total number of transferrin receptors than their normal counterparts. This data was supported by Northern blot analysis, which showed equivalent transferrin receptor mRNA expression in HTLV-I-infected and uninfected cells. Functional analysis revealed a marked defect in 59Fe-transferrin internalization in the HTLV-I-infected cells. Furthermore, the HTLV-I-infected cells showed markedly decreased transferrin receptor phosphorylation and internalization in response to active phorbol ester. Thus the data demonstrate that in peripheral blood T cells, HTLV-I infection is accompanied by surface transferrin receptor overexpression secondary to subcellular redistribution and defective internalization.
mesh_terms: D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D017977:Deltaretrovirus / Q000502:physiology*; D006800:Deltaretrovirus Infections / Q000209:etiology / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011990:Receptors, Transferrin / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D008562:Membrane Glycoproteins; D011990:Receptors, Transferrin; D013755:Tetradecanoylphorbol Acetate