Surfactant protein A binds to HIV and inhibits direct infection of CD4+ cells, but enhances dendritic cell-mediated viral transfer.
The identification of surfactant protein A (SP-A) as an important innate immune factor of the lungs, amniotic fluid, and the vaginal tract suggests that it could play an important role during various stages of HIV disease progression and transmission. Therefore, we examined whether SP-A could bind to HIV and also had any effect on viral infectivity. Our data demonstrate that SP-A binds to HIV in a calcium-dependent manner that is inhibitable by mannose and EDTA. Affinity capture of the HIV viral lysate reveals that SP-A targets the envelope glycoprotein of HIV (gp120), which was confirmed by ELISA using recombinant gp120. Digestion of gp120 with endoglycosidase H abrogates the binding of SP-A, indicating that the high mannose structures on gp120 are the target of the collectin. Infectivity studies reveal that SP-A inhibits the infection of CD4+ T cells by two strains of HIV (BaL, IIIB) by >80%. Competition assays with CD4 and mAbs F105 and b12 suggest that SP-A inhibits infectivity by occlusion of the CD4-binding site. Studies with dendritic cells (DCs) demonstrate that SP-A enhances the binding of gp120 to DCs, the uptake of viral particles, and the transfer of virus from DCs to CD4+ T cells by >5-fold at a pH representative of the vaginal tract. Collectively, these results suggest that SP-A acts as a dual modulator of HIV infection by protecting CD4+ T cells from direct infection but enhancing the transfer of infection to CD4+ T cells mediated by DCs.
Medical Research Council Immunochemistry Unit, Department of Biochemistry, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Gaurav D
GD
Gaiha
Tao
T
Dong
Nades
N
Palaniyar
Daniel A
DA
Mitchell
Kenneth B M
KB
Reid
Howard W
HW
Clark
D000293:Adolescent; D000328:Adult; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D006224:Cricetinae; D003713:Dendritic Cells / Q000276:immunology*; D006678:HIV / Q000276:immunology* / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008358:Mannose / Q000378:metabolism; D009844:Oligosaccharides / Q000378:metabolism; D011485:Protein Binding; D037662:Pulmonary Surfactant-Associated Protein A / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
D015699:HIV Envelope Protein gp120; D009844:Oligosaccharides; D037662:Pulmonary Surfactant-Associated Protein A; D011994:Recombinant Proteins; D008358:Mannose