Differential mucosal susceptibility in HIV-1 transmission and infection

HIV infection occurs primarily through mucosal surfaces, indicating that protection at mucosal sites may be crucial in prevention and treatment. The host innate and adaptive immune elements provide a level of protection, which differs between mucosal compartments, and appears to be most successful in the oral environment, where transmission is rare. In addition to the distinct oral mucosal architecture and cellular constituents, oral fluids, unlike other mucosal secretions, are rarely a vehicle for HIV infection. Multiple soluble factors may contribute to this antiviral activity, including neutralizing antibodies, secretory leukocyte protease inhibitor (SLPI), antiviral peptides such as defensins and cystatins, glycoproteins including thrombospondin and lactoferrin, and complement components. Understanding the antiviral activities of these and other potential resistance factors is becoming increasingly important in attempts to design treatments in the era of HAART resistance. In this regard, the mechanism of anti-HIV action of SLPI has recently been further elucidated by the discovery of its binding protein/receptor, which plays a key role in the infection of macrophages and may consequently be a novel therapeutic target. Continued elucidation of the unique features of mucosal HIV immunology is essential for understanding HIV pathogenesis and for developing effective vaccines and therapeutics.