The Role of HIV-1-Encoded microRNAs in Viral Replication

Abstract

microRNAs (miRNAs) are small non-coding RNAs (sncRNAs) that play an important role in the life cycle of human viruses. We sought to characterize human immunodeficiency virus 1 (HIV-1)-encoded miRNAs and determine their role in viral replication. Initially, a bioinformatic analysis was used to predict HIV-1-encoded miRNAs. Next, a representative number of these predicted sequences were verified using a miRNA microarray chip, reverse transcription PCR (RT-PCR), and the deep sequencing of RNA extracted from HIV-1-infected cells. Eight HIV-1-encoded sncRNA sequences conforming to the criteria that define miRNAs were identified in HIV-1-infected immortalized T cells and human primary CD4+ lymphocytes; five of the eight sequences have not been previously reported. Deep sequencing validated the presence of these virus-encoded miRNA sequences and uncovered large numbers of atypical sncRNA sequences, lacking characteristics of conventional miRNAs. We named these sequences small RNAs (smRNAs). The overexpression of four candidate HIV-1-encoded miRNAs and silencing of two smRNAs significantly increased HIV-1 viral replication. Our study uncovered novel HIV-1-encoded sncRNAs that, upon deregulated expression, alter viral titers in HIV-1-infected cells, suggesting that miRNAs and smRNAs play an important role in regulating viral replication. Future studies may reveal the function of HIV-1-encoded sncRNAs and their possible implications for diagnosis and treatment.

Human and Viral microRNA Expression in Acute and Chronic HIV Infections

“…This could be due to the fact that viral miRNAs are more recently discovered and the current databases for their recognition by NGS data have difficulty being updated promptly. For example, the database used in the present study could not detect some recently discovered HIV-encoded miRNAs described in [ 42 ].…”