IFN[beta] Protects Neurons from Damage in a Murine Model of HIV-1 Associated Brain Injury

Infection with human immunodeficiency virus-1 (HIV-1) causes brain injury. Type I interferons (IFNα/β) are critical mediators of any anti-viral immune response and IFNβ has been implicated in the temporary control of lentiviral infection in the brain. Here we show that transgenic mice expressing HIV...

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Bibliographic Details
Published in:Scientific reports 2017-04, Vol.7, p.46514
Main Authors: Thaney, Victoria E, O'neill, Alan M, Hoefer, Melanie M, Maung, Ricky, Sanchez, Ana B, Kaul, Marcus
Format: Article
Language:English
Subjects:
Age
Animal models
Antibodies
Antiviral agents
Astrocytes
Brain injury
CCL4 protein
Central nervous system
Cortex
Dendrites
Glycoprotein gp120
Hippocampus
HIV
Human immunodeficiency virus
Immune response
Interferon
mRNA
Neuroprotection
Neurotoxicity
Rodents
Toxicity
Transgenic mice
Traumatic brain injury
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Summary:Infection with human immunodeficiency virus-1 (HIV-1) causes brain injury. Type I interferons (IFNα/β) are critical mediators of any anti-viral immune response and IFNβ has been implicated in the temporary control of lentiviral infection in the brain. Here we show that transgenic mice expressing HIV-1 envelope glycoprotein 120 in their central nervous system (HIVgp120tg) mount a transient IFNβ response and provide evidence that IFNβ confers neuronal protection against HIVgp120 toxicity. In cerebrocortical cell cultures, neuroprotection by IFNβ against gp120 toxicity is dependent on IFNα receptor 1 (IFNAR1) and the β-chemokine CCL4, as IFNAR1 deficiency and neutralizing antibodies against CCL4, respectively, abolish the neuroprotective effects. We find in vivo that IFNβ mRNA is significantly increased in HIVgp120tg brains at 1.5, but not 3 or 6 months of age. However, a four-week intranasal IFNβ treatment of HIVgp120tg mice starting at 3.5 months of age increases expression of CCL4 and concomitantly protects neuronal dendrites and pre-synaptic terminals in cortex and hippocampus from gp120-induced damage. Moreover, in vivo and in vitro data suggests astrocytes are a major source of IFNβ-induced CCL4. Altogether, our results suggest exogenous IFNβ as a neuroprotective factor that has potential to ameliorate in vivo HIVgp120-induced brain injury.
ISSN:2045-2322
DOI:10.1038/srep46514