Role of cell surface glycosaminoglycans of human T cells in human immunodeficiency virus type-1 (HIV-1) infection.
To investigate the role of cell surface glycosaminoglycans (GAGs), including heparan sulfate (HS), on HIV-1 infection in human T cells, HIV-1 binding and infection were determined after treatment of T-cell lines and CD4+ T cells from normal peripheral blood mononuclear cells (PBMC) with GAG-degrading enzyme or a GAG metabolic sulfation inhibitor. Heparitinase I (hep I) and sodium chlorate prevented binding of HIV-1/IIIB to MT-4 cells as revealed by indirect immunofluorescence procedures, thereby inhibiting infection. Hep I was less effective in the binding inhibition of the macrophage-tropic strain HIV-1/SF162 than that of the T-cell line-tropic strain HIV-1/IIIB. The binding of HIV-1/SF162 was about 100-fold less dependent on cell surface HS than HIV-1/IIIB. Human HTLV-I positive T-cell lines expressed more HS than HTLV-I negative T-cell lines or normal CD4+ T cells when stained with anti-HS mAbs against either native or heparitinase-treated HS. With the exception of endo-beta-galactosidase (endo-beta-gal), GAG-degrading enzymes, including hep I, chondroitinase ABC (chon ABC), chondroitinase AC II (chon AC II) and keratanase, did not prevent the binding of HIV-1/IIIB to CD4+ T cells from normal PBMC. These results indicate that the cell surface HS of human T cells participates in HIV-1 infection by facilitating HIV-1/IIIB binding to MT-4 cells. In particular, the sulfation of HS chains is critical. Since the expression of cell surface HS varies among T cells, which are not consistently sensitive to hep I treatment in HIV-1 binding inhibition, other GAG-like molecules may also be involved.
Ohshiro
Y
Y
Department of Microbiology, Tokyo Medical and Dental University School of Medicine, Japan.
Murakami
T
T
Matsuda
K
K
Nishioka
K
K
Yoshida
K
K
Yamamoto
N
N
D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000821:virology*; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry; D002704:Chlorates / Q000494:pharmacology; D002808:Chondroitin Lyases / Q000494:pharmacology; D019084:Fluorescent Antibody Technique, Indirect; D006025:Glycosaminoglycans / Q000502:physiology*; D006026:Glycoside Hydrolases; D015497:HIV-1 / Q000502:physiology*; D006497:Heparan Sulfate / Q000032:analysis / Q000502:physiology*; D006801:Humans; D011133:Polysaccharide-Lyases / Q000494:pharmacology; D013601:T-Lymphocytes / Q000737:chemistry / Q000821:virology*; D001616:beta-Galactosidase / Q000494:pharmacology
D002704:Chlorates; D002808:Chondroitin Lyases; D006025:Glycosaminoglycans; D006026:Glycoside Hydrolases; D006497:Heparan Sulfate; D011133:Polysaccharide-Lyases; D001616:beta-Galactosidase; C026093:keratan-sulfate endo-1,4-beta-galactosidase; C021349:heparitinsulfate lyase; C032706:sodium chlorate