Date Published:
2019 04

Publication Type:
Journal Article

Authors:

T.A. Premeaux
M.L. D'Antoni
M. Abdel-Mohsen
S.K. Pillai
K.J. Kallianpur
B.K. Nakamoto
M. Agsalda-Garcia
B. Shiramizu
C.M. Shikuma
M. Gisslén
R.W. Price
V. Valcour
L.C. Ndhlovu

Secondary:
J Neurovirol

Volume:
25

Pagination:
150-161

Issue:
2

PMID:
30478799

URL:
https://pubmed.ncbi.nlm.nih.gov/30478799

DOI:
10.1007/s13365-018-0696-3

Keywords:
Adult;Age Factors;Anti-HIV Agents;Antigens, CD;Antigens, Differentiation, Myelomonocytic;Antiretroviral Therapy, Highly Active;Biomarkers;Case-Control Studies;Central Nervous System;Cognition;External;Female;Galectins;HIV Infections;HIV-1;Humans;Male;Middle Aged;Neopterin;Neuropsychological Tests;Receptors, Cell Surface;RNA, Viral;Viremia

Abstract:
<p>We previously reported that galectin-9 (Gal-9), a soluble lectin with immunomodulatory properties, is elevated in plasma during HIV infection and induces HIV transcription. The link between Gal-9 and compromised neuronal function is becoming increasingly evident; however, the association with neuroHIV remains unknown. We measured Gal-9 levels by ELISA in cerebrospinal fluid (CSF) and plasma of 70 HIV-infected (HIV+) adults stratified by age (older > 40 years and younger < 40 years) either ART suppressed or with detectable CSF HIV RNA, including a subgroup with cognitive assessments, and 18 HIV uninfected (HIV-) controls. Gal-9 tissue expression was compared in necropsy brain specimens from HIV- and HIV+ donors using gene datasets and immunohistochemistry. Among older HIV+ adults, CSF Gal-9 was elevated in the ART suppressed and CSF viremic groups compared to controls, whereas in the younger group, Gal-9 levels were elevated only in the CSF viremic group (p < 0.05). CSF Gal-9 positively correlated with age in all groups (p < 0.05). CSF Gal-9 tracked with CSF HIV RNA irrespective of age (β = 0.33; p < 0.05). Higher CSF Gal-9 in the older viremic HIV+ group correlated with worse neuropsychological test performance scores independently of age and CSF HIV RNA (p < 0.05). Furthermore, CSF Gal-9 directly correlated with myeloid activation (CSF-soluble CD163 and neopterin) in both HIV+ older groups (p < 0.05). Among HIV+ necropsy specimens, Gal-9 expression was increased in select brain regions compared to controls (p < 0.05). Gal-9 may serve as a novel neuroimmuno-modulatory protein that is involved in driving cognitive deficits in those aging with HIV and may be valuable in tracking cognitive abnormalities.</p>