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Review
, 32 (1), 7-14

Type I Interferons in NeuroHIV

Affiliations
Review

Type I Interferons in NeuroHIV

Victoria E Thaney et al. Viral Immunol.

Abstract

Infection with Human Immunodeficiency Virus (HIV)-1 continues to cause HIV-associated neurocognitive disorders despite combined antiretroviral therapy. Interferons (IFNs) are important for any antiviral immune response, but the lasting production of IFNα causes exhaustive activation leading eventually to progression to AIDS. Expression of IFNα in the HIV-exposed central nervous system has been linked to cognitive impairment and inflammatory neuropathology. In contrast, IFNβ exerts anti-inflammatory effects, appears to control, at least temporarily, lentiviral infection in the brain and provides neuroprotection. The dichotomy of type I IFN effects on HIV-1 infection and the associated brain injury will be discussed in this review, because the underlying mechanisms require further investigation to allow harnessing these innate immune factors for therapeutic purposes.

Keywords: HIV-1; IFNα/β; NeuroAIDS; neurodegeneration; neuroprotection; type I interferon.

Conflict of interest statement

No competing financial interests exist.

Figures

<b>FIG. 1.</b>
FIG. 1.
Schematic model of the effects of IFNα and IFNβ in the HIV-infected brain and HAND. HIV-1 reaches the brain apparently soon after peripheral infection and resides in perivascular MΦ and microglia. These cell types are the primary sites of productive viral infection in the CNS, although all neural cell types can express the HIV coreceptors, CCR5 and CXCR4. HIV-infected and uninfected stimulated MΦ and microglia produce neurotoxins that damage neurons presumably engaging various receptors and mechanisms, all culminating in synaptic and dendritic injury and eventually neuronal apoptosis. HIV-infected MΦ and microglia may, at least temporarily, produce IFNα and IFNβ. CCL2 released by astrocytes, however, can suppress IFNα production by MΦ and microglia. IFNα and IFNβ can interact with all cells in the CNS since all express the two IFNAR subunits. Stimulation with IFNα and IFNβ generally induces ISGs and an antiviral state in all cell types. However, the spectrum of ISGs induced may be different for each type I IFN. IFNα seems to promote inflammatory processes and directly and/or indirectly compromise neuronal function and thus may contribute to the development of HAND. In contrast, IFNβ seems to overall limit inflammatory processes and contribute to neuroprotection by counteracting injurious mechanisms. In vivo, exogenous IFNβ can be delivered to the brain through intranasal application. CNS, central nervous system; HAND, HIV-associated neurocognitive disorder; IFN, interferon; IFNAR, IFN-α/β receptor; ISG, IFN-stimulated gene; MΦ, macrophages.

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