Secretory Leukocyte Protease Inhibitor Binds to Annexin II, a Cofactor for Macrophage HIV-1 Infection

Ma, Ge; Greenwell-Wild, Teresa; Lei, Kejian; Jin, Wenwen; Swisher, Jennifer; Hardegen, Neil; Wild, Carl T.; Wahl, Sharon M.

Secretory leukocyte protease inhibitor (SLPI), originally identified as a serine protease inhibitor at portals of pathogen entry and in mucosal fluids (1) , has more recently been associated with multiple functions relevant to innate host defense (2) (3) (4) (5) (6) (7) (8) (9) . One of the first novel non-antiprotease functions identified for SLPI was its ability to inhibit HIV-1 infection of macrophages, which appeared to be effected through interaction with unidentified host cell molecules and not the virus (2, 3) . In addition to CD4, macrophages express CCR5 and CXCR4 that function as HIV-1 envelope gp120 coreceptors (10) , and once colonized by HIV-1, can function as stable reservoirs of the virus, thereby facilitating transmission of HIV-1 to CD4 Ï© lymphocytes (11, 12) . Persistent evidence favors the existence of additional cofactors for binding and/or entry of HIV-1, including components of the host cell membrane acquired during viral budding (13) . Among these host-derived constituents in the viral envelope is the phospholipid, phosphatidylserine (PS; reference 14) , which predicts a potential interactive molecule on the receptive host cell that may facilitate virus binding, entry, and/or fusion.