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Molecular Neurobiology

, Volume 55, Issue 3, pp 1905–1914 | Cite as

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

  • C. Sanfilippo
  • M.R. Pinzone
  • D. Cambria
  • A. Longo
  • M. Palumbo
  • R. Di Marco
  • F. Condorelli
  • G. Nunnari
  • L. Malaguarnera
  • M. Di Rosa
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.

Keywords

OAS1 OAS2 OAS3 OASL HAD HAND HIV 

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

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Section of Neurosciences, Department G.F. IngrassiaUniversity of CataniaCataniaItaly
  2. 2.Department of Pathology and Laboratory Medicine, School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  3. 3.Department of Biomedical and Biotechnological SciencesUniversity of CataniaCataniaItaly
  4. 4.Department of Medicine and Health SciencesUniversity of MoliseCampobassoItaly
  5. 5.Department of Pharmacological SciencesUniversità del Piemonte OrientaleNovaraItaly
  6. 6.Unit of Infectious Diseases, Department of Clinical and Experimental MedicineUniversity of MessinaMessinaItaly

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