Epithelial uptake and transport of cell-free human immunodeficiency virus type 1 and gp120-coated microparticles.
Cell-free human immunodeficiency virus type 1 (HIV-1) can be taken up and released by a monolayer of primary human gingival cells and remain infectious for CD4+ cells. Virus-sized latex particles covalently coated with purified native HIV-1 envelope glycoprotein gp120 are also transported through the primary epithelial cells. This process is significantly stimulated by increasing the intracellular cyclic AMP (cAMP) concentration. Inhibition experiments with mannan and alpha-methyl-mannopyranoside indicated that mannosyl groups are involved in the interaction between gp120 and gingival cells. An increase of cellular oligomannosyl receptors by incubation with the mannosidase inhibitor deoxymannojirimycin augmented transcellular transport of the gp120-coated particles. The results suggest that infectious HIV can penetrate gingival epithelia by a cAMP-dependent transport mechanism involving interaction of the lectin-like domain of gp120 and mannosyl residues on glycoproteins on the mucosal surface. Penetration of HIV could be inhibited by soluble glycoconjugates present in oral mucins.
Kage
A
A
Universitätsklinikum Rudolf Virchow, Institut für Klinische Chemie und Biochemie, Berlin, Germany. akage@ukrv.de
Shoolian
E
E
Rokos
K
K
Ozel
M
M
Nuck
R
R
Reutter
W
W
Köttgen
E
E
Pauli
G
G
D001692:Biological Transport; D002461:Cell Line, Transformed; D002474:Cell-Free System; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects / Q000821:virology*; D005881:Gingiva / Q000166:cytology / Q000821:virology; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism* / Q000472:pathogenicity; D006801:Humans; D008297:Male; D008351:Mannans / Q000378:metabolism / Q000494:pharmacology; D008766:Methylmannosides / Q000378:metabolism / Q000494:pharmacology; D008863:Microspheres; D009077:Mucins / Q000378:metabolism / Q000494:pharmacology; D011134:Polysaccharides / Q000378:metabolism; D015728:Receptors, HIV / Q000378:metabolism
D015699:HIV Envelope Protein gp120; D008351:Mannans; D008766:Methylmannosides; D009077:Mucins; D011134:Polysaccharides; D015728:Receptors, HIV; C008466:methylmannoside