Pj. Swart et al., THE IN-VITRO ANTI-HIV EFFICACY OF NEGATIVELY CHARGED HUMAN SERUM-ALBUMIN IS ANTAGONIZED BY HEPARIN, AIDS research and human retroviruses, 13(8), 1997, pp. 677-683
Succinylated human serum albumin (Suc-HSA) was synthesized by treating
human serum albumin with succinic anhydride, Among similar proteins a
nd neo(glyco)proteins tested, Suc-HSA exhibits a pronounced net negati
ve charge, a feature that largely contributes to its efficacy against
replication of human immunodeficiency virus type 1 (HIV-1), To assess
further the antiviral effect of Suc-HSA, the effect on HIV-1 replicati
on was studied in the presence of whole human plasma, Pretreatment of
MT2 cells with Suc-HSA was more efficacious than direct Suc-HSA treatm
ent of HIV prior to addition to the cells, No changes in the antiviral
effect of Suc-HSA were observed in tissue culture medium, 30% plasma,
or whole plasma when CPDA-1 (citrate-phosphate-dextrose-adenine 1) wa
s used as the anticoagulant, However, a dramatic decrease (greater tha
n 99%) in the antiviral activity was observed when these experiments w
ere performed in plasma prepared from blood using heparin as anticoagu
lant, The antagonistic effect by heparin was observed both in the case
that heparin was added prior to or after addition of Suc-HSA to the t
est system, In the present study we demonstrate that heparin largely r
educes Suc-HSA activity on HIV replication in the same concentration i
n which if affects binding of Suc-HSA to the envelope protein gp120 an
d in particular its V3 domain, In the same concentration range, hepari
n reduced binding of Suc-HSA to MT4 cells, another HTLV-I-transformed
cell line, It is concluded that heparin can displace Suc-HSA from its
binding sites on hybrid lymphoid cells as well as on HIV-1 particles,
Therefore, we conclude that both the binding to cells and to virus con
tribute to the potent anti-HIV-1 effect, The fact that heparin and hep
arin degradation products antagonize Suc-HSA without having a signific
ant anti-HIV-1 effect indicates that the anticoagulant acts as a relat
ively weak partial inhibitor.