Elevated cerebrospinal fluid Galectin-9 is associated with central nervous system immune activation and poor cognitive performance in older HIV-infected individuals

J Neurovirol. 2019 Apr;25(2):150-161. doi: 10.1007/s13365-018-0696-3. Epub 2018 Nov 26.


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.

Keywords: Biomarkers; Cognitive disorders; Galectin-9; HIV; Neuroinflammation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Anti-HIV Agents / therapeutic use
  • Antigens, CD / cerebrospinal fluid
  • Antigens, CD / genetics*
  • Antigens, Differentiation, Myelomonocytic / cerebrospinal fluid
  • Antigens, Differentiation, Myelomonocytic / genetics*
  • Antiretroviral Therapy, Highly Active
  • Biomarkers / cerebrospinal fluid
  • Case-Control Studies
  • Central Nervous System / drug effects
  • Central Nervous System / metabolism
  • Central Nervous System / physiopathology
  • Central Nervous System / virology*
  • Cognition / drug effects
  • Cognition / physiology
  • Female
  • Galectins / cerebrospinal fluid
  • Galectins / genetics*
  • HIV Infections / cerebrospinal fluid
  • HIV Infections / drug therapy
  • HIV Infections / immunology
  • HIV Infections / virology*
  • HIV-1 / genetics
  • HIV-1 / pathogenicity
  • Humans
  • Male
  • Middle Aged
  • Neopterin / cerebrospinal fluid
  • Neuropsychological Tests
  • RNA, Viral / cerebrospinal fluid
  • RNA, Viral / genetics*
  • Receptors, Cell Surface / genetics*
  • Viremia / cerebrospinal fluid
  • Viremia / drug therapy
  • Viremia / immunology
  • Viremia / virology*


  • Anti-HIV Agents
  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Biomarkers
  • CD163 antigen
  • Galectins
  • LGALS9 protein, human
  • RNA, Viral
  • Receptors, Cell Surface
  • Neopterin