Susceptibility to highly sulphated glycosaminoglycans of human immunodeficiency virus type 1 replication in peripheral blood lymphocytes and monocyte-derived macrophages cell cultures.
In the search for new drugs against human immunodeficiency virus type 1 (HIV-1), the replication of III(B) and BaL strains, and of seven primary isolates from AIDS patients, cultured both in peripheral blood lymphocytes (PBLs) and in monocyte-derived macrophages (MACs), was investigated in the presence of two dermatan sulphate and heparin at 10 microg/ml. The three polysaccharides effectively inhibited the replication of III(B) in PBLs and of BaL in MACs, while producing either a slight inhibition or an unexpected large increase in the replication of the seven primary isolates, especially in MAC cultures. In one case, stimulation was found in PBLs and, at lower doses, also with BaL in MACs. Co-receptor use, adaptation to C8166 T cell line, partial sequence of the gp120 V3 loop, variation in positive charge distribution and number of potential glycosylation sites along the V3 loop were assessed for each strain. No explanation could be found for the different susceptibility of the viruses to the polysaccharides. Their presence probably brings about both inhibitory and stimulatory effects, the final outcome depending on the virus, cells and polysaccharide.
Bartolini
Barbara
B
Istituto di Cristallografia, Sezione di Roma, CNR, PO Box 10, I-00016 Monterotondo Stazione, Rome, Italy.
Di Caro
Antonino
A
Cavallaro
Rosaria A
RA
Liverani
Lino
L
Mascellani
Giuseppe
G
La Rosa
Giuseppina
G
Marianelli
Cinzia
C
Muscillo
Michele
M
Benedetto
Arrigo
A
Cellai
Luciano
L
D000595:Amino Acid Sequence; D002478:Cells, Cultured; D003871:Dermatan Sulfate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D014644:Genetic Variation; D006025:Glycosaminoglycans / Q000494:pharmacology*; D015699:HIV Envelope Protein gp120 / Q000096:biosynthesis / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008264:Macrophages / Q000821:virology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000096:biosynthesis / Q000235:genetics; D014779:Virus Replication / Q000187:drug effects
D006025:Glycosaminoglycans; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D003871:Dermatan Sulfate; D006493:Heparin