Human immunodeficiency virus type 1 Tat binds to Candida albicans, inducing hyphae but augmenting phagocytosis in vitro

Abstract

SUMMARYTat, the human immunode®ciency 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 dif®cult 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.

Oral candidiasis profile of the Indonesian HIV-infected pediatric patients at UPIPI Dr. Soetomo General Hospital, Surabaya, Indonesia

“…SAP is an excellent extracellular hydrolytic enzyme that is capable of destroying mucosal cell wall of the oral cavity to facilitate adhesion and invasion of C. albicans. This interaction favors oral candidiasis to manifest in the oral cavity [27]. Some patients were also accompanied by symptoms of xerostomia.…”

Candida and candidiasis in HIV-infected patients

“…Enhanced Sap production is detected in vivo and increases with advancing stages of HIV infection. Intriguingly, this phenomenon could derive from the capacity of the virus to stably bind to the fungus and/or by Sap induction by the HIVenvelope (GP160) or other viral proteins such as Tat [92,93]. Whether overexpression of virulence traits or even selection of more virulent fungal genotypes is due to the HIV binding itself or induction by HIV proteins or by other events, has not been established.…”

Phagocytic Activity in Human Immunodeficiency Virus Type 1 Infection

“…In addition, we demonstrated a significant inhibition exerted by Nef protein on Candida albicans macrophagic phagocytosis and killing, depending on oxidative processes (82). Conversely, Tat protein is able to bind Candida albicans through its RGD motif (Arg-Gly-Asp) and to induce hyphae production, a phenomenon that seems to increase the in vitro phagocytosis of the yeast (38).…”