Interplay between HIV-1 infection and host microRNAs

• Published in: Nucleic acids research Vol. 40; no. 5; pp. 2181 - 2196
• Main Authors: Sun, Guihua, Li, Haitang, Wu, Xiwei, Covarrubias, Maricela, Scherer, Lisa, Meinking, Keith, Luk, Brian, Chomchan, Pritsana, Alluin, Jessica, Gombart, Adrian F., Rossi, John J.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.03.2012
• Subjects: Binding Sites; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - virology; Cell Line; Gene Expression Profiling; Gene Expression Regulation; HIV Long Terminal Repeat; HIV-1 - genetics; Human immunodeficiency virus 1; Humans; MicroRNAs - chemistry; MicroRNAs - metabolism; nef Gene Products, Human Immunodeficiency Virus - genetics; RNA; RNA Interference
• ISSN: 0305-1048; 1362-4962
• DOI: 10.1093/nar/gkr961

Using microRNA array analyses of in vitro HIV-1-infected CD4+ cells, we find that several host microRNAs are significantly up- or downregulated around the time HIV-1 infection peaks in vitro. While microRNA-223 levels were significantly enriched in HIV-1-infected CD4+CD8− PBMCs, microRNA-29a/b, microRNA-155 and microRNA-21 levels were significantly reduced. Based on the potential for microRNA binding sites in a conserved sequence of the Nef-3′-LTR, several host microRNAs potentially could affect HIV-1 gene expression. Among those microRNAs, the microRNA-29 family has seed complementarity in the HIV-1 3′-UTR, but the potential suppressive effect of microRNA-29 on HIV-1 is severely blocked by the secondary structure of the target region. Our data support a possible regulatory circuit at the peak of HIV-1 replication which involves downregulation of microRNA-29, expression of Nef, the apoptosis of host CD4 cells and upregulation of microRNA-223.