Journal of Antivirals & Antiretrovirals
Open Access

Involvement of miRNAs in the development of HIV-1-associated neurocognitive disorders

International Conference and Exhibition on VIROLOGY

5-7 September 2011 Baltimore, USA

Bassel E Sawaya

Scientific Tracks Abstracts: JAA

Abstract :

Over the last decade, small non-coding RNA molecules such as microRNAs (miRNAs) have emerged as critical regulators in the expression and function of eukaryotic genomes. It has been suggested that viral infections and neurological disease outcome may also be shaped by the infl uence of small RNAs. Th is has prompted us to suggest that HIV infection alters the endogenous miRNA expression patterns, thereby contributing to neuronal deregulation and AIDS dementia. Th erefore, using primary cultures and neuronal cell lines, we examined the impact of a viral protein (HIV-1 Tat and Vpr) on the expression of miRNAs due to its characteristic features such as release from the infected and taken up by non-infected cells. Using microRNA array assay, we demonstrated that Tat and Vpr deregulate the levels of several miRNAs. Interestingly, miR-34a was among the most highly induced miRNAs in Tator Vpr-treated neurons. Tat and Vpr also decrease the levels of miR-34a target genes such as CREB protein as shown by real-time PCR. Th e eff ect of Tat and/or Vpr was neutralized in the presence of anti-miR-34a. Using in situ hybridization assay, we found that the levels of miR-34a increases in Tat- and in Vpr-transgenic mice when compared to the parental mice. Th erefore, we conclude that deregulation of neuronal functions by HIV-1 Tat or Vpr protein is miRNAsdependent.