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MicroRNA regulation and its effects on cellular transcriptome in Human Immunodeficiency Virus-1 (HIV-1) infected individuals with distinct viral load and CD4 cell counts

Duskova, K and Nagilla, P and Le, HS and Iyer, P and Thalamuthu, A and Martinson, J and Bar-Joseph, Z and Buchanan, W and Rinaldo, C and Ayyavoo, V (2013) MicroRNA regulation and its effects on cellular transcriptome in Human Immunodeficiency Virus-1 (HIV-1) infected individuals with distinct viral load and CD4 cell counts. BMC Infectious Diseases, 13 (1).

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Abstract

Background: Disease progression in the absence of therapy varies significantly in HIV-1 infected individuals. Both viral and host cellular molecules are implicated; however, the exact role of these factors and/or the mechanism involved remains elusive. To understand how microRNAs (miRNAs), which are regulators of transcription and translation, influence host cellular gene expression (mRNA) during HIV-1 infection, we performed a comparative miRNA and mRNA microarray analysis using PBMCs obtained from infected individuals with distinct viral load and CD4 counts.Methods: RNA isolated from PBMCs obtained from HIV-1 seronegative and HIV-1 positive individuals with distinct viral load and CD4 counts were assessed for miRNA and mRNA profile. Selected miRNA and mRNA transcripts were validated using in vivo and in vitro infection model.Results: Our results indicate that HIV-1 positive individuals with high viral load (HVL) showed a dysregulation of 191 miRNAs and 309 mRNA transcripts compared to the uninfected age and sex matched controls. The miRNAs miR-19b, 146a, 615-3p, 382, 34a, 144 and 155, that are known to target innate and inflammatory factors, were significantly upregulated in PBMCs with high viral load, as were the inflammatory molecules CXCL5, CCL2, IL6 and IL8, whereas defensin, CD4, ALDH1, and Neurogranin (NRGN) were significantly downregulated. Using the transcriptome profile and predicted target genes, we constructed the regulatory networks of miRNA-mRNA pairs that were differentially expressed between control, LVL and HVL subjects. The regulatory network revealed an inverse correlation of several miRNA-mRNA pair expression patterns, suggesting HIV-1 mediated transcriptional regulation is in part likely through miRNA regulation.Conclusions: Results from our studies indicate that gene expression is significantly altered in PBMCs in response to virus replication. It is interesting to note that the infected individuals with low or undetectable viral load exhibit a gene expression profile very similar to control or uninfected subjects. Importantly, we identified several new mRNA targets (Defensin, Neurogranin, AIF) as well as the miRNAs that could be involved in regulating their expression through the miRNA-mRNA interaction. © 2013 Duskova et al.; licensee BioMed Central Ltd.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Duskova, K
Nagilla, P
Le, HS
Iyer, P
Thalamuthu, A
Martinson, Jjmartins@pitt.eduJMARTINS
Bar-Joseph, Z
Buchanan, W
Rinaldo, CRINALDO@pitt.eduRINALDO
Ayyavoo, Vvelpandi@pitt.eduVELPANDI
Date: 30 May 2013
Date Type: Publication
Journal or Publication Title: BMC Infectious Diseases
Volume: 13
Number: 1
DOI or Unique Handle: 10.1186/1471-2334-13-250
Schools and Programs: School of Medicine > Infectious Diseases and Microbiology
Refereed: Yes
Date Deposited: 30 Sep 2016 14:28
Last Modified: 02 Feb 2019 15:55
URI: http://d-scholarship.pitt.edu/id/eprint/29720

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