Anti-HIV type 1 activity of sulfated derivatives of dextrin against primary viral isolates of HIV type 1 in lymphocytes and monocyte-derived macrophages.
The anti-HIV-1 activity of sulfated derivatives of dextrin was tested in activated peripheral blood mononuclear cells and in monocyte-derived macrophages using low-passage syncytium-inducing and non-syncytium-inducing primary viral isolates of HIV-1. All four compounds blocked infection in a dose-dependent manner. Dextrin 2-sulfate blocked infection with a 90% inhibitory concentration (IC90) of 69 microg ml(-1). The IC90 for dextrin 3-sulfate was 50 microg ml(-1) and for dextrin 6-sulfate was 14 microg ml(-1). Increasing the number of sulfate groups to three per glucan molecule (dextrin 2-, 3-, and 6-sulfate) did not reduce the IC90 further (13 microg ml(-1)) compared to dextrin 6-sulfate. There was no significant difference in the concentration required to block infection of activated peripheral blood mononuclear cells when compared with monocyte-derived macrophages, irrespective of whether low-passage syncytium-inducing or non-syncytium-inducing primary viral isolates of HIV-1 were used. Dextrin 2-sulfate and dextrin 6-sulfate also reduced the transmission of HIV-1 in experiments performed using peripheral blood mononuclear cells from HIV-1-positive patients by 6- to 251-fold in a limiting dilution tissue culture infectious dose assay. Sulfated dextrins were not toxic to either primary lymphocytes or macrophages at the concentrations tested. Having previously shown that the cell surface binding of sulfated dextrins is dependent on the position of the negatively charged sulfate groups, we now show that their anti-HIV-1 activity in primary lymphocytes and macrophages is also dependent on the same arrangement. A phase I/II clinical trial of dextrin 2-sulfate is now in progress.
Javan
C M
CM
Department of Infectious Diseases, Royal Postgraduate Medical School, London, UK.
Gooderham
N J
NJ
Edwards
R J
RJ
Davies
D S
DS
Shaunak
S
S
D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003912:Dextrins / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000187:drug effects / Q000821:virology; D008264:Macrophages / Q000187:drug effects / Q000821:virology
D019380:Anti-HIV Agents; D003912:Dextrins; C091377:dextrin 2-sulfate