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Journal article

Galectin-9 is rapidly released during acute HIV-1 infection and remains sustained at high levels despite viral suppression even in elite controllers.

Abstract:
Galectin-9 (Gal-9) is a β-galactosidase-binding lectin that promotes apoptosis, tissue inflammation, and T cell immune exhaustion, and alters HIV infection in part through engagement with the T cell immunoglobulin mucin domain-3 (Tim-3) receptor and protein disulfide isomerases (PDI). Gal-9 was initially thought to be an eosinophil attractant, but is now known to mediate multiple complex signaling events that affect T cells in both an immunosuppressive and inflammatory manner. To understand the kinetics of circulating Gal-9 levels during HIV infection we measured Gal-9 in plasma during HIV acquisition, in subjects with chronic HIV infection with differing virus control, and in uninfected individuals. During acute HIV infection, circulating Gal-9 was detected as early as 5 days after quantifiable HIV RNA and tracked plasma levels of interleukin (IL)-10, tumor necrosis factor (TNF)-α, and IL-1β. In chronic HIV infection, Gal-9 levels positively correlated with plasma HIV RNA levels (r=0.29; p=0.023), and remained significantly elevated during suppressive antiretroviral therapy (median: 225.3 pg/ml) and in elite controllers (263.3 pg/ml) compared to age-matched HIV-uninfected controls (54 pg/ml). Our findings identify Gal-9 as a novel component of the first wave of the cytokine storm in acute HIV infection that is sustained at elevated levels in virally suppressed subjects and suggest that Gal-9:Tim-3 crosstalk remains active in elite controllers and antiretroviral (ARV)-suppressed subjects, potentially contributing to ongoing inflammation and persistent T cell dysfunction.
Publication status:
Published

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Publisher copy:
10.1089/aid.2014.0004

Authors


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Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Jenner Institute
Role:
Author


Publisher:
Mary Ann Liebert Inc.
Journal:
AIDS research and human retroviruses More from this journal
Volume:
30
Issue:
7
Pages:
654-664
Publication date:
2014-07-01
DOI:
EISSN:
1931-8405
ISSN:
0889-2229


Language:
English
Pubs id:
pubs:463272
UUID:
uuid:c1be35e1-e176-46b6-a5a5-36ae1886c5ba
Local pid:
pubs:463272
Source identifiers:
463272
Deposit date:
2014-06-17

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