Chronic HIV-1 Tat and HIV Reduce Rbfox3/NeuN: Evidence for Sex- Related Effects

Author(s): Yun Kyung Hahn, Ruturaj R. Masvekar, Ruqiang Xu, Kurt F. Hauser, Pamela E. Knapp

Journal Name: Current HIV Research

Volume 13 , Issue 1 , 2015

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Abstract:

The NeuN antibody has been widely used to identify and quantify neurons in normal and disease situations based on binding to a nuclear epitope in most types of neurons. This epitope was recently identified as the RNA-binding, feminizing locus on X-3 (Rbfox3), a member of the larger, mammalian Fox1 family of RNA binding proteins. Fox1 proteins recognize a unique UGCAUG mRNA motif and regulate alternative splicing of precursor mRNA to control post-transcriptional events important in neuronal differentiation and central nervous system development. Recent clinical findings show that Rbfox3/NeuN gene dosage is altered in certain human neurodevelopmental disorders, and redistribution has been noted in HIV+ tissue. We hypothesized that HIV-1 Tat might affect Rbfox3/NeuN expression, and examined this question in vivo using inducible transgenic mice, and in vitro using human mesencephalic-derived neurons. Rbfox3/NeuN expression and localization in HIV+ basal ganglia and hippocampus was also examined. Chronic Tat exposure reduced Rbfox3/NeuN protein levels and increased cytoplasmic localization, similar to the effect of HIV exposure. Cytoplasmic Rbfox3/NeuN signal has occasionally been reported, although the meaning or function of cytoplasmic versus nuclear localization remains speculative. Importantly, Rbfox3/NeuN reductions were more significant in male mice. Although Rbfox3/NeuN-expressing cells were significantly decreased by Tat exposure, stereology showed that Nissl+ neuron numbers remained normal. Thus, loss of Rbfox3/NeuN may relate more to functional change than to neuron loss. The effects of Tat by itself are highly relevant to HIV+ individuals maintained on antiretroviral therapy, since Tat is released from infected cells even when viral replication is inhibited.

Keywords: Human, male, NeuroAIDS, neurodegeneration, stereology, transgenic.

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Article Details

VOLUME: 13
ISSUE: 1
Year: 2015
Page: [10 - 20]
Pages: 11
DOI: 10.2174/1570162X13666150311163733

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