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

Lund, Nicole ; Olsson, Martin L LU orcid ; 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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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
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
2016-04-01 12:36:10
date last changed
2024-10-09 16:20:25
@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}},
  doi          = {{10.1182/blood-2008-03-143396}},
  volume       = {{113}},
  year         = {{2009}},
}