Surfactant protein A binds to HIV and inhibits direct infection of CD4+ cells but enhances dendritic cell-mediated viral transfer
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
601-609
Gaiha, Gaurav D.
f6408afc-1449-4689-b991-170729232946
Dong, Tao
942142fb-76a5-430c-85ae-17155db4263d
Palaniyar, Nades
262890ae-b2b1-4f9b-8129-08f8bcd6a399
Mitchell, Daniel A.
d489622a-19e8-43a0-87cd-ba866f5212c2
Reid, Kenneth B.M.
74c6c3e3-d682-446d-b159-b635e6056e4e
Clark, Howard W.
70550b6d-3bd7-47c6-8c02-4f43f37d5213
1 July 2008
Gaiha, Gaurav D.
f6408afc-1449-4689-b991-170729232946
Dong, Tao
942142fb-76a5-430c-85ae-17155db4263d
Palaniyar, Nades
262890ae-b2b1-4f9b-8129-08f8bcd6a399
Mitchell, Daniel A.
d489622a-19e8-43a0-87cd-ba866f5212c2
Reid, Kenneth B.M.
74c6c3e3-d682-446d-b159-b635e6056e4e
Clark, Howard W.
70550b6d-3bd7-47c6-8c02-4f43f37d5213
Gaiha, Gaurav D., Dong, Tao, Palaniyar, Nades, Mitchell, Daniel A., Reid, Kenneth B.M. and Clark, Howard W.
(2008)
Surfactant protein A binds to HIV and inhibits direct infection of CD4+ cells but enhances dendritic cell-mediated viral transfer.
Journal of Immunology, 181 (1), .
(PMID:18566427)
Abstract
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
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Published date: 1 July 2008
Organisations:
Faculty of Medicine, Infection Inflammation & Immunity
Identifiers
Local EPrints ID: 72735
URI: http://eprints.soton.ac.uk/id/eprint/72735
ISSN: 0022-1767
PURE UUID: f5dc2374-dd78-4645-afe0-a197c60efc18
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Date deposited: 22 Feb 2010
Last modified: 13 Mar 2024 21:38
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Contributors
Author:
Gaurav D. Gaiha
Author:
Tao Dong
Author:
Nades Palaniyar
Author:
Daniel A. Mitchell
Author:
Kenneth B.M. Reid
Author:
Howard W. Clark
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