Low anticoagulant heparin retains anti-HIV type 1 activity in vitro.
Heparin is a potent inhibitor of HIV-1 replication, in addition to being a well-established inhibitor of blood coagulation. The major anticoagulant activity of heparin results from binding to the plasma protein antithrombin (AT). The high-affinity binding site for AT is a specific pentasaccharide sequence that is of low abundance and completely absent from the majority of heparin chains. We have examined the anti-HIV-1 activity of both conventional and low molecular weight heparins fractionated according to affinity for AT. The high- and low-affinity fractions, despite differing markedly in anticoagulant activity, are identical in their ability to bind to the envelope glycoprotein of HIV-1, and in their inhibitory effect on HIV-1 replication in vitro (EC50 1 and 8 micrograms/ml for conventional and low molecular weight fractions, respectively). Our study shows that the anti-HIV activity of heparin is independent of its antithrombin-mediated inhibition of coagulation proteases. Therefore, heparin preparations retaining full anti-HIV-1 activity in vitro but with greatly reduced anticoagulant activity may be readily produced for further clinical investigation in the prophylaxis and therapy of HIV infection.
Coombe
D R
DR
Institute for Child Health Research, Perth, Western Australia.
Harrop
H A
HA
Watton
J
J
Mulloy
B
B
Barrowcliffe
T W
TW
Rider
C C
CC
D000925:Anticoagulants / Q000494:pharmacology*; D000990:Antithrombin III / Q000378:metabolism; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006493:Heparin / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008970:Molecular Weight; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
D000925:Anticoagulants; D000998:Antiviral Agents; D000990:Antithrombin III; D006493:Heparin