Secretory leukocyte protease inhibitor binds to annexin II, a cofactor for macrophage HIV-1 infection.
The distribution of secretory leukocyte protease inhibitor (SLPI) at entry portals indicates its involvement in defending the host from pathogens, consistent with the ability of SLPI to inhibit human immunodeficiency virus (HIV)-1 infection by an unknown mechanism. We now demonstrate that SLPI binds to the membrane of human macrophages through the phospholipid-binding protein, annexin II. Based on the recent identification of human cell membrane phosphatidylserine (PS) in the outer coat of HIV-1, we define a novel role for annexin II, a PS-binding moiety, as a cellular cofactor supporting macrophage HIV-1 infection. Moreover, this HIV-1 PS interaction with annexin II can be disrupted by SLPI or other annexin II-specific inhibitors. The PS-annexin II connection may represent a new target to prevent HIV-1 infection.
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Oral Infection and Immunity Branch, NIDCR, NIH, 30 Convent Dr., MSC4352, Building 30, Room 320, Bethesda, MD 20892, USA.
Greenwell-Wild
Teresa
T
Lei
Kejian
K
Jin
Wenwen
W
Swisher
Jennifer
J
Hardegen
Neil
N
Wild
Carl T
CT
Wahl
Sharon M
SM
D017306:Annexin A2 / Q000378:metabolism*; D015153:Blotting, Western; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D017931:DNA Primers; D005434:Flow Cytometry; D015658:HIV Infections / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D008264:Macrophages / Q000378:metabolism* / Q000821:virology; D013058:Mass Spectrometry; D008856:Microscopy, Fluorescence; D010718:Phosphatidylserines / Q000378:metabolism*; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053481:Secretory Leukocyte Peptidase Inhibitor
D017306:Annexin A2; D017931:DNA Primers; D010718:Phosphatidylserines; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D034741:RNA, Small Interfering; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor