Comparative Expression Profile of miRNA and mRNA in Primary Peripheral Blood Mononuclear Cells Infected with Human Immunodeficiency Virus (HIV-1)

Abstract

Host cells respond to exogenous infectious agents such as viruses, including HIV-1. Studies have evaluated the changes associated with virus infection at the transcriptional and translational levels of the cellular genes involved in specific pathways. While this approach is useful, in our view it provides only a partial view of genome-wide changes. Recently, technological advances in the expression profiling at the microRNA (miRNA) and mRNA levels have made it possible to evaluate the changes in the components of multiple pathways. To understand the role of miRNA and its interplay with host cellular gene expression (mRNA) during HIV-1 infection, we performed a comparative global miRNA and mRNA microarray using human PBMCs infected with HIV-1. The PBMCs were derived from multiple donors and were infected with virus generated from the molecular clone pNL4-3. The results showed that HIV-1 infection led to altered regulation of 21 miRNAs and 444 mRNA more than 2-fold, with a statistical significance of p<0.05. Furthermore, the differentially regulated miRNA and mRNA were shown to be associated with host cellular pathways involved in cell cycle/proliferation, apoptosis, T-cell signaling, and immune activation. We also observed a number of inverse correlations of miRNA and mRNA expression in infected PBMCs, further confirming the interrelationship between miRNA and mRNA regulation during HIV-1 infection. These results for the first time provide evidence that the miRNA profile could be an early indicator of host cellular dysfunction induced by HIV-1.

Data Submission and Quality in Microarray-Based MicroRNA Profiling

“…However, in some cases, partial data were available for review or full datasets were uploaded post-publication, either at my request or at the behest of the journal. In the cases (15,17–19) I examined most closely, the original data were found to provide limited support for the conclusions of the articles (Supplemental Text file, Section III). One of these articles has since been retracted (17,29).…”

“…Additionally, post-publication requests for missing data were made for multiple articles, including but not limited to Huang, et al (16), Gupta, et al (17), Rahman, et al (18), and Mohan, et al (19). When data were made available, they were accessed and re-analyzed if possible, first following the authors’ described methods as faithfully as possible and then using different approaches, for example, as outlined in previous publications (20–23).…”

P1–234: Circulating miRNA biomarkers for Alzheimer's disease

“…This means that while a single miRNAs can target multiple mRNAs, a single mRNA can also be targeted by multiple miRNAs [81]. The relationship of a single miRNA to potentially target as many as 200 different mRNA targets is well documented [82] [83], but there is also evidence of single mRNAs being targets of multiple miRNAs [84]. To put this complex ''many to many'' relationship in a biological context, a comprehensive analysis of all miRNA targets suggested that a set of miRNA targets regulated by a single miRNA generally constitutes a biological network of functionally-associated molecules in human cells [85].…”

Gamma-Retroviral Vector Design for the Co-Expression of Artificial microRNAs and Therapeutic Proteins

“…As backbones for the amiR sequences we chose micro-RNA previously shown to be abundantly expressed in human lymphocytes, specifically miR-142, miR-146b, miR-150, miR-155, miR-16, and miR-223 [27][28][29][30]. Using a representative siRNA sequence targeted to TIPE2, we constructed 11 individual vectors with the amiRs inserted into one of two restriction enzyme sites within the intron of the tCD34 vector (Fig.…”