Molecular Characterization of the HIV-1 gp41-/gp160-binding protein of candida albicans

The commensal relationship between man and Candida, which has evolved over millions of years, has recently taken a sharp turn. In the century of immunosuppression and AIDS, Candida represents the major cause of opportunistic fungal infection in the immunocompromised host. HIV-positive subjects suffer from recurrent oral candidiasis but only when the aggravation of the HIV infection affects the phagocytic network, potentially lethal systemic fungal infections may occur. Mucocutaneous candidiasis appears to be readily explained by the acquired T-cell deficiency, however, it remains an open question why it develops in HIV-infected patients but not necessarily in all inherited T-cell disorders. Two additional observations prompted us to investigate whether there is, in addition, a direct interaction between HIV-1 envelope proteins and C. albicans. First, HIV-1 gp41 contains four regions with partial sequence homology to human C3. It was therefore considered possible that gp41 might react with natural receptors of C3, such as complement receptors (CR1, CR2, CR3, CR4). Independently from the sequence homology of gp41 to C3, these have been considered to represent a second receptor for HIV-1. Second, such complement receptor analogues have been described on C. albicans. Detailed investigations revealed that HIV-1 does bind to C. albicans. This binding appears to occur via C3 homologous regions on the virus and the CR3-like molecule on the yeast. We proposed that oral candidiasis in HIV-1 infected subjects may be augmented or may even be initiated by direct interaction between C. albicans and HIV-1 or HIV-1-infected cells. This is supported by the finding that treatment of C. albicans with gp160, but not with gp120, augments both release and activity of Candida secreted aspartate proteinase, a candidal virulence factor, but also strongly inhibits phagocytosis by granulocytes. As preliminary experiments have shown that the CR3-like molecule described by Hostetter and co-workers does not represent the HIV binding molecule the aim of this study therefore is to characterise the HIV-gp41/gp160-binding protein on the molecular level by generating a cDNA library of C. albicans and by probing the library primarily with oligonucleotides, obtained from N-terminal sequencing of purified gp41-/gp160-binding protein. A second aim is to assess the relevance of the HIV binding molecule for adhesion on epithelial cells, a major fungal virulence factor.