Human immunodeficiency virus type 1 Tat binds to Candida albicans, inducing hyphae but augmenting phagocytosis in vitro.
Tat, the human immunodeficiency virus type 1 (HIV-1) transactivating protein, binds through its RGD-motif to human integrin receptors. Candida albicans, the commonest cause of mucosal candidiasis in subjects infected with HIV-1, also possesses RGD-binding capacity. The present study reveals that Tat binds to C. albicans but not to C. tropicalis. Tat binding was markedly reduced by laminin and to a lesser extent by a complement C3 peptide containing the RGD motif, but not by a control peptide. The outgrowth of C. albicans was accelerated following binding of Tat, but phagocytosis of opsonized C. albicans was also increased after Tat binding. Thus, Tat binding promotes fungal virulence by inducing hyphae but may also reduce it by augmenting phagocytosis. The net effect of Tat in vivo is difficult to judge but in view of the many disease-promoting effects of Tat we propose that accelerating the formation of hyphae dominates over the augmentation of phagocytosis.
Gruber
A
A
Institute for Hygiene and Social Medicine, University of Innsbruck, Ludwig Boltzmann-Institute for AIDS-Research, Innsbruck, Austria. andreas_gruber@dfci.harvard.edu
Lell
C P
CP
Speth
C
C
Stoiber
H
H
Lass-Flörl
C
C
Sonneborn
A
A
Ernst
J F
JF
Dierich
M P
MP
Würzner
R
R
D000074183:ATPases Associated with Diverse Cellular Activities; D001667:Binding, Competitive; D002175:Candida / Q000378:metabolism; D002176:Candida albicans / Q000378:metabolism* / Q000472:pathogenicity; D018929:Cell Culture Techniques; D003176:Complement C3 / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007797:Laminin / Q000494:pharmacology; D008024:Ligands; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects*; D046988:Proteasome Endopeptidase Complex; D014774:Virulence
D003176:Complement C3; D004268:DNA-Binding Proteins; D007797:Laminin; D008024:Ligands; D046988:Proteasome Endopeptidase Complex; D000074183:ATPases Associated with Diverse Cellular Activities; C064757:PSMC3 protein, human