title: Role of O-glycosylation and expression of CD43 and CD45 on the surfaces of effector T cells in human T cell leukemia virus type 1 cell-to-cell infection.
abstract: We used replication-dependent retroviral vectors to identify cell surface antigens involved in the cell-to-cell transmission of human T cell leukemia virus type 1 (HTLV-1). We generated monoclonal antibodies (MAbs) against Jurkat T cells and selected several IgM MAbs that strongly inhibited HTLV-1 but not human immune deficiency virus type 1 (HIV-1) cell-to-cell infection. These MAbs recognized the so-called Tn antigen (GalNAcα1-O-Ser/Thr) that arises on Jurkat cells from a mutation in the T-synthase-specific chaperone Cosmc and the consequent loss of O-glycan elongation. Anti-Tn MAbs precipitated two major O-glycan carrier proteins, CD43 and CD45, and caused a strong aggregation of Jurkat cells. The restoration of O-glycosylation in Jurkat cells by stably transducing the wild-type Cosmc gene resulted in a 3- to 4-fold increase in the level of surface expression of CD43 and enhanced HTLV-1 transmission 10-fold in comparison to that of parental cells. The short hairpin RNA (shRNA) knockdown of CD43 or CD45 expression in Jurkat-Cosmc, HBP-ALL, and CEM T cells decreased HTLV-1 infection severalfold. The knockdown of CD45 in Jurkat cells severely reduced both HTLV-1 and HIV-1 infections, but Cosmc coexpression partially rescued infection. HTLV-1 proteins, which assembled in small patches on Jurkat cells, formed large clusters on the surface of Jurkat-Cosmc cells. These data indicate that large aggregates of HTLV-1 assemblies are more infectious than multiple clustered virions. We suggest that heavily O-glycosylated CD43 and CD45 molecules render cells less adhesive, prevent inappropriate cell-cell contacts, and favor the assembly of HTLV-1 particles into large, highly infectious structures on the surface of T cells.
authors.affiliation: Laboratory of Immunochemistry, Institute of Immunology, Moscow, Russia. dvmazurov@yandex.ru
authors.forename: Dmitriy
authors.initials: D
authors.lastname: Mazurov
authors.forename: Anna
authors.initials: A
authors.lastname: Ilinskaya
authors.forename: Gisela
authors.initials: G
authors.lastname: Heidecker
authors.forename: Alexander
authors.initials: A
authors.lastname: Filatov
mesh_terms: D015870:Gene Expression; D006031:Glycosylation; D015490:HTLV-I Infections / Q000235:genetics* / Q000378:metabolism* / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000378:metabolism*; D051917:Leukosialin / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism* / Q000821:virology
chemical_list: D051917:Leukosialin; D017493:Leukocyte Common Antigens