Characterization of human immunodeficiency virus type 1 resistant to modified cyclodextrin sulphate (mCDS71) in vitro

Drug resistance of human immunodeficiency virus type 1 (HIV) to modified cy clodextrin sulphate (mCDS71) has been analysed with respect to both the in vitro appearance of resistance to the compound and the mechanism of the acq uisition of resistance. Resistant strains could be obtained in all three st rains (NL432, KK-1 and A018) tested after serial passages in MT-4 cells wit h a gradual increase of the concentration of mCDS71. Cross-resistance both to mCDS71 and dextran sulphate 8000 was observed. As a result of sequencing analysis of the gp120 V3-C5 region of resistant strains, the mechanism of resistance can be explained in several ways: (i) substitution of sugar chai n-binding amino acids, N and S; (ii) three to five amino acid deletion in V 4 loop; and (iii) several mutations in V3 and V4 regions. The real cause of the resistance may be a combination of these three mechanisms. The results suggest that the target of mCDS71 is relatively widely distributed on the viral surface glycoprotein.