It has been reported that hepatitis C virus (HCV) may be lymphotropic in the setting of human immunodeficiency virus type 1 (HIV-1) coinfection. The present study was undertaken to determine the phenotype of lymphoid cells harboring replicating HCV in HIV-1-positive subjects. By means of highly strand-specific thermostable enzyme Tth-based reverse-transcriptase polymerase chain reaction, the presence of viral RNA-negative strand was sought in different subpopulations of peripheral blood mononuclear cells from 10 HIV-positive patients. HCV RNA-negative strand was most commonly present in monocytes/macrophages (4 cases), followed by CD8+ and CD4+ lymphocytes (2 cases) and CD19+ cells (1 case). In 2 cases that were further analyzed, viral-negative strand remained detectable in monocytes/macrophages cultured for 3 weeks. Moreover, monocyte/macrophage- and serum-derived viral sequences differed in the 5' untranslated region. These findings imply that, in HIV-infected subjects, HCV may replicate in the same cells as HIV-1, which raises the possibility of direct interactions between these pathogens.

Very complex glycosphingolipids with A, H and I blood-group activities were isolated from human erythrocyte membranes. The membranes were obtained from erythrocytes of blood group A, A2 a n d 0 respectively. A general formula for the antigens is:(where Fuc is fucose, Gal is galactose, GlcNAc is N-acetylglucosamine and Glc is glucose) with values of y2 ranging from 10-27. A-active preparations contain additionally 2-3 residues of N-acetylgalactosamine. In view of the unusual complexity of these compounds they were designated poly(glycosy1)ceramides (formerly megaloglycolipids). Individual poly(glycosy1)ceramide fractions were isolated from A erythrocytes and were found to differ by about 8 glycosyl residues per molecule forming a series of compounds with 22, 30, 38, 51 and 59 glycosyl residues per mole. Structural studies indicate that the main sequence of poly(glycosy1)ceramides consists of the residues of galactopyranose and 2-deoxy-2-acetamidoglucopyranose substituted at 3 and 4 position respectively. These residues are probably alternating. N-Acetylglucosamine substituted at 3 position was not found in poly-(glycosy1)ceramides. Branches of poly(glycosy1)ceramides originate from 3 and 6 position of galactopyranosyl residues. The number of branches is proportional to the degree of molecular complexity. In poly(glycosy1)ceramides isolated from A and A2 erythrocytes the branches are terminated with the following structures GalNAc CI 1 +3 [Fuc CI 1 '21 Gal; Fuc CI 1 -i2 Gal and Gal (presumably Gal 1 -+4 GlcNAc). In poly(glycosy1)ceramides from A cells the total number of A and H-active structures per average molecule of 30-35 glycosyl residues amounts to 2.1 and 1.2 respectively while the number of terminal galactose structures is 1.8. For poly(glycosy1)ceramides from A2 erythrocytes the corresponding figures are 0.75, 3.5, and 2.1 respectively.Poly(glycosy1)ceramides from 0 cells comprise about 3.8 H-active structures and 1.8 terminal galactopyranosyl residues. In poly(glycosy1)ceramides with high "n" values the number of terminal galactose structures is increased. These fractions display high blood-group I activity. However, the removal of terminal galactose with P-galactosidase affects I-activity only slightly.

Fucose-containing glycolipids with H and B blood group activity as well as sialic acid and glucosamine-contaig glycolipid were isolated from human erythrocytes. The sequences and linkages of carbohydrate residues in these glycolipids were determined by partial acid hydrolysis, periodate oxidation and methylation studies. Anomeric linkage were ascribed to those materials on the basis of their optical rotations, infrared spectra, susceptibility to enzymes and immunological activities.

New synthetic protocol for the preparation of nucleoside 5'-(N-aryl)phosphoramidate monoesters 4 was developed. It consisted of a condensation of the corresponding nucleoside 5'-H-phosphonates with aromatic- or heteroaromatic amines promoted by diphenyl phosphorochloridate, followed by oxidation of the produced H-phosphonamidates with iodine/water. 5'-(N-Aryl)phosphoramidate monoesters derived from 3'-azido-3'-deoxythymidine (AZT) or 2',3'-dideoxyuridine (ddU) nucleosides and various aromatic and heteroaromatic amines were evaluated as potential anti-HIV drugs. It was found that these compounds act most likely as pronucleotides and that some of them have therapeutic indices superior to those of the reference AZT.

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