OBJECTIVE: To successfully treat a mouse model of HIV encephalitis (HIVE) with a novel interferonalpha
(IFNα)
inhibitor. BACKGROUND: Despite available antiretroviral treatment, HIVassociated
neurocognitive disorders (HAND)
remain highly prevalent. IFNα has been identified as a neurotoxin that plays a prominent role in HAND and HIVE
pathology. Ongoing studies have suggested that B18R, a novel IFNα inhibitor, can prevent HIVE pathology.
DESIGN/METHODS: Severe Combined Immunodeficiency (SCID) mice were injected with HIVinfected
or uninfected
(Controls; n=8) human monocytes intracerebrally (IC). Starting the same day as IC injections of human cells HIVE
mice were treated subcutaneously with either saline (n=8) or B18R (50 mcg/day) (n=8) for 10 days. Mice were
sacrificed and brains extracted. Brains were sectioned and stained for B18R, neuronal integrity (MAP2), HIV, human
macrophages, mouse mononuclear phagocytes, and astrocytes. RNA was extracted from these brains for real time
PCR analysis. Primarily IFNα related genes were measured. RESULTS: Immunostaining for B18R in systemically
treated HIVE/SCID mice suggested that B18R crosses the blood brain barrier. Realtime
PCR indicated that B18R
treatment results in decreased gene expression associated with IFNα signaling in the brain. Mice treated with B18R
had decreased mouse mononuclear phagocytes in brain and significant retention of neuronal arborization compared to
untreated HIVE/SCID mice. CONCLUSIONS: These results suggest that systemic B18R treatment prevents key
features of HIVE pathology. B18R may be a viable addition to combined antiretroviral therapy (cART) in the treatment
of HAND. Ongoing studies are evaluating whether the addition of B18R to cART is superior to each therapy alone.

Title

Neurology

Publisher

American Academy of Neurology

Publisher Country

United States of America

Indexing

Thomson Reuters

Impact Factor

8.166

Publication Type

Prtinted only

Volume

82

Year

2014

Pages

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