Mechanism of the inhibitory effect of curdlan sulfate on HIV-1 infection in vitro.
To study the mechanism by which sulfated polysaccharides with 1,3-beta-D-glucan as a main chain exert anti-HIV-1 activity, we analyzed the effects of curdlan sulfate (CRDS) on HIV-1 infection of SupT-1 cells and peripheral blood mononuclear cells. CRDS had no effect on virions inhibited weakly HIV-1 attachment to cells, and had to be present for 24 hr to achieve protection. Lack of HIV-1 DNA corresponding to the gag region in cells incubated with the virus and CRDS and inhibition of infection after addition of 2',3'-dideoxyinosine to cells treated with CRDS and HIV-1 for less than 24 hr suggest that CRDS delays events that precede and/or include reverse transcription. Analysis of the effect of CRDS on binding of HIV-1 neutralizing antibodies to gp 120 demonstrated that both the continuous epitopes on the V3 loop and the discontinuous CD4 binding site of gp 120 represent targets for CDRS. This interaction of CRDS with functional gp 120 domains suggests that CRDS interferes with the membrane fusion process during HIV-1 infection. Concentrations of CRDS that were protective against infection with T cell- and macrophage-tropic HIV-1 isolates had less suppressive effects on T cell function in comparison with the related compound, dextran sulfate.
Jagodzinski
P P
PP
Department of Microbiology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Wiaderkiewicz
R
R
Kurzawski
G
G
Kloczewiak
M
M
Nakashima
H
H
Hyjek
E
E
Yamamoto
N
N
Uryu
T
T
Kaneko
Y
Y
Posner
M R
MR
D000838:Anions; D000998:Antiviral Agents; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000382:microbiology*; D002459:Cell Fusion / Q000187:drug effects; D002942:Circular Dichroism; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D017931:DNA Primers / Q000737:chemistry; D005936:Glucans / Q000494:pharmacology*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects*; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis; D008969:Molecular Sequence Data; D000071228:Polyelectrolytes; D011108:Polymers; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects; D014771:Virion / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects*; D047071:beta-Glucans
D000838:Anions; D000998:Antiviral Agents; D017931:DNA Primers; D005936:Glucans; D015699:HIV Envelope Protein gp120; D007376:Interleukin-2; D000071228:Polyelectrolytes; D011108:Polymers; D047071:beta-Glucans; C063130:curdlan sulfate