Mannan-binding lectin (MBL) is an effector molecule of the innate immune system found in human serum that binds to carbohydrate and mediates recognition and killing of pathogens. Although the human immunodeficiency virus (HIV) would appear to be a good target of MBL due the unusually high level of high mannose glycosylation of gpl20, this has not been well studied. Our research - group found that MBL binds to a wide range of HIV isolates including primary isolates. Thus, MBL has several highly desirable features of an anti-HIV effector molecule; 1) it binds to a wide range of virus isolates; 2) binding of MBL to HIV is likely via the unusual cluster of high mannose microgram levels. These features of MBL suggest it mediates anti-viral activity in vivo and inforrnation gained about its interaction with HIV will lead to a better understanding of both the role of innate immunity during HIV infection and the importance of carbohydrate structures on HIV. The overall goals of this study are to determine the mechanism of interaction between MBL and HIV and to determine methods to enhance the anti-HIV activity of MBL. These goals will be accomplished by the following specific aims: Deterrnine the type and location of carbobydrates responsible for high-level binding of HIV- 1 to MBL. 2. Investigate factors that affect the interaction between HIV and MBL. 3. Utilize inhibitors of glycosylation to enhance biological effects of MBL. Exarnine the interaction of MBL with anti-viral antibodies in mediating anti-viral effects. Deterrnine the interaction of HIV-1 with MBL in vivo.
