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The human P-k histo-blood group antigen provides protection against HIV-1 infection

Lund, Nicole; Olsson, Martin L LU ; Ramkumar, Stephanie; Sakac, Darinka; Yahalom, Vered; Levene, Cyril; Hellberg, Åsa LU ; Ma, Xue-Zhong; Binnington, Beth and Jung, Daniel, et al. (2009) In Blood 113(20). p.4980-4991
Abstract
Several human histo-blood groups are glycosphingolipids, including P/P1/P-k. Glycosphingolipids are implicated in HIV-host-cell-fusion and some bind to HIV-gp120 in vitro. Based on our previous studies on Fabry disease, where P-k accumulates and reduces infection, and a soluble P-k analog that inhibits infection, we investigated cell surface-expressed P-k in HIV infection. HIV-1 infection of peripheral blood-derived mononuclear cells (PBMCs) from otherwise healthy persons, with blood group P-1(k), where P-k is overexpressed, or blood group p, that completely lacks P-k, were compared with draw date-matched controls. Fluorescence-activated cell sorter analysis and/or thin layer chromatography were used to verify P-k levels. P-1(k) PBMCs were... (More)
Several human histo-blood groups are glycosphingolipids, including P/P1/P-k. Glycosphingolipids are implicated in HIV-host-cell-fusion and some bind to HIV-gp120 in vitro. Based on our previous studies on Fabry disease, where P-k accumulates and reduces infection, and a soluble P-k analog that inhibits infection, we investigated cell surface-expressed P-k in HIV infection. HIV-1 infection of peripheral blood-derived mononuclear cells (PBMCs) from otherwise healthy persons, with blood group P-1(k), where P-k is overexpressed, or blood group p, that completely lacks P-k, were compared with draw date-matched controls. Fluorescence-activated cell sorter analysis and/or thin layer chromatography were used to verify P-k levels. P-1(k) PBMCs were highly resistant to R5 and X4 HIV-1 infection. In contrast, p PBMCs showed 10- to 1000-fold increased susceptibility to HIV-1 infection. Surface and total cell expression of P-k, but not CD4 or chemokine coreceptor expression, correlated with infection. Pk liposome-fused cells and CD4(+) HeLa cells manipulated to express high or low P-k levels confirmed a protective effect of P-k. We conclude that P-k expression strongly influences susceptibility to HIV-1 infection, which implicates P-k as a new endogenous cell-surface factor that may provide protection against HIV-1 infection. (Blood. 2009;113:4980-4991) (Less)
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published
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Blood
volume
113
issue
20
pages
4980 - 4991
publisher
American Society of Hematology
external identifiers
  • wos:000266090700025
  • scopus:66549127485
ISSN
1528-0020
DOI
10.1182/blood-2008-03-143396
language
English
LU publication?
yes
id
27915819-4f27-49e4-9081-7c50b9e61761 (old id 1425719)
date added to LUP
2009-07-01 13:51:32
date last changed
2017-10-09 09:42:47
@article{27915819-4f27-49e4-9081-7c50b9e61761,
  abstract     = {Several human histo-blood groups are glycosphingolipids, including P/P1/P-k. Glycosphingolipids are implicated in HIV-host-cell-fusion and some bind to HIV-gp120 in vitro. Based on our previous studies on Fabry disease, where P-k accumulates and reduces infection, and a soluble P-k analog that inhibits infection, we investigated cell surface-expressed P-k in HIV infection. HIV-1 infection of peripheral blood-derived mononuclear cells (PBMCs) from otherwise healthy persons, with blood group P-1(k), where P-k is overexpressed, or blood group p, that completely lacks P-k, were compared with draw date-matched controls. Fluorescence-activated cell sorter analysis and/or thin layer chromatography were used to verify P-k levels. P-1(k) PBMCs were highly resistant to R5 and X4 HIV-1 infection. In contrast, p PBMCs showed 10- to 1000-fold increased susceptibility to HIV-1 infection. Surface and total cell expression of P-k, but not CD4 or chemokine coreceptor expression, correlated with infection. Pk liposome-fused cells and CD4(+) HeLa cells manipulated to express high or low P-k levels confirmed a protective effect of P-k. We conclude that P-k expression strongly influences susceptibility to HIV-1 infection, which implicates P-k as a new endogenous cell-surface factor that may provide protection against HIV-1 infection. (Blood. 2009;113:4980-4991)},
  author       = {Lund, Nicole and Olsson, Martin L and Ramkumar, Stephanie and Sakac, Darinka and Yahalom, Vered and Levene, Cyril and Hellberg, Åsa and Ma, Xue-Zhong and Binnington, Beth and Jung, Daniel and Lingwood, Clifford A. and Branch, Donald R.},
  issn         = {1528-0020},
  language     = {eng},
  number       = {20},
  pages        = {4980--4991},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {The human P-k histo-blood group antigen provides protection against HIV-1 infection},
  url          = {http://dx.doi.org/10.1182/blood-2008-03-143396},
  volume       = {113},
  year         = {2009},
}