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OAS Gene Family Expression Is Associated with HIV-Related Neurocognitive Disorders

Molecular Neurobiology volume 55, pages 1905–1914 (2018)Cite this article

Abstract

HIV-associated neurocognitive disorders are common in HIV-infected individuals, even in the combination antiretroviral therapy (c-ART) era. Several mechanisms are involved in neuronal damage, including chronic inflammation immune activation. Mammalian 2′-5′-oligoadenylate synthetase (OAS) genes are produced in response to interferon (IFN), mainly by monocytes, and exert their antiviral functions by activation of RNase L that degrades viral and cellular RNAs. In this study, we aimed at exploring OAS gene family RNA expression in simian immunodeficiency virus encephalitis (SIVE), in HIV-associated neurocognitive disorders (HAND), and in HIV-associate dementia (HAD). We analyzed three microarray datasets obtained from the NCBI in order to assess the expression levels of OAS gene family network in brain biopsies of macaques with SIVE vs uninfected animals, as well as post-mortem brain of individuals with HAND (on or off ART) vs uninfected controls and three brain regions of HIV-infected individuals with both neurocognitive impairment (HAD) and encephalitis (HIVE). All OAS genes were upregulated both in SIVE and in HAND. OAS expression was significantly higher in high-viremic individuals; increased expression levels persisted in cART subjects when compared to healthy controls. OAS gene network analysis showed that several genes belonging to the type I IFN pathway, especially CXCL10 and IFIT3, were similarly upregulated in SIVE/HAND. Furthermore, we identified a significant upregulation of OAS gene family RNA expression in basal ganglia, white matter, and frontal cortex of HIV-1, HAD, and HAD/HIVE patients compared to healthy subjects. OAS gene family expression is increased in brain sections from individuals with HAND, HAD, and HIVE as well as macaques with SIVE. OAS family expression is likely to be induced by IFN as a consequence of viral replication in the CNS. Its long-term upregulation may contribute to the chronic inflammatory status and neurocognitive impairment we still observe in virologically suppressed individuals on c-ART.

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Abbreviations

c-ART:

Combination antiretroviral therapy

HAART:

Highly active anti-retroviral therapy

AIDS:

Acquired immune deficiency syndrome

CNS:

Central nervous system

HIV:

Human immunodeficiency virus

SIV:

HIV/simian immunodeficiency virus

SIVE:

Simian immunodeficiency virus encephalitis

HAND:

HIV-associated neurocognitive disorders

HAD:

HIV-infected with neurocognitive impairment or HIV associate dementia

ANI:

Asymptomatic neurocognitive impairment

HIVE:

HIV encephalitis

BBB:

Blood-brain barrier

CSF:

Cerebrospinal fluid

CXCL10:

C-X-C motif chemokine 10

FDR:

False discovery rate

IFIT3:

Interferon-induced protein with tetratricopeptide repeats 3

OAS1:

2′-5′-Oligoadenylate synthetase 1

OAS2:

2′-5′-Oligoadenylate synthetase 2

OAS3:

2′-5′-Oligoadenylate synthetase 3

OASL:

2′-5′-Oligoadenylate synthetase-like

MeV:

MultiExperiment Viewer

IQR:

Interquartile range

BVL:

Brain viral load

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Author information

Affiliations

  1. Section of Neurosciences, Department G.F. Ingrassia, University of Catania, Via Santa Sofia 78, 95123, Catania, Italy

    C. Sanfilippo

  2. Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania, Philadelphia, USA

    M.R. Pinzone

  3. Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy

    D. Cambria, A. Longo, M. Palumbo, L. Malaguarnera & M. Di Rosa

  4. Department of Medicine and Health Sciences, University of Molise, Campobasso, Italy

    R. Di Marco

  5. Department of Pharmacological Sciences, Università del Piemonte Orientale, A. Avogadro, 28100, Novara, Italy

    F. Condorelli

  6. Unit of Infectious Diseases, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy

    G. Nunnari

Authors
  1. C. Sanfilippo
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  2. M.R. Pinzone
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  3. D. Cambria
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  4. A. Longo
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  5. M. Palumbo
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  6. R. Di Marco
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  7. F. Condorelli
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  8. G. Nunnari
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  9. L. Malaguarnera
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  10. M. Di Rosa
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Corresponding author

Correspondence to M. Di Rosa.

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Sanfilippo, C., Pinzone, M., Cambria, D. et al. OAS Gene Family Expression Is Associated with HIV-Related Neurocognitive Disorders. Mol Neurobiol 55, 1905–1914 (2018). https://doi.org/10.1007/s12035-017-0460-3

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  • DOI: https://doi.org/10.1007/s12035-017-0460-3

Keywords

  • OAS1
  • OAS2
  • OAS3
  • OASL
  • HAD
  • HAND
  • HIV