Human cellular microRNA hsa-miR-29a interferes with viral nef protein expression and HIV-1 replication.
BACKGROUND
Cellular miRNAs play an important role in the regulation of gene expression in eukaryotes. Recently, miRNAs have also been shown to be able to target and inhibit viral gene expression. Computational predictions revealed earlier that the HIV-1 genome includes regions that may be potentially targeted by human miRNAs. Here we report the functionality of predicted miR-29a target site in the HIV-1 nef gene.


RESULTS
We find that the human miRNAs hsa-miR-29a and 29b are expressed in human peripheral blood mononuclear cells. Expression of a luciferase reporter bearing the nef miR-29a target site was decreased compared to the luciferase construct without the target site. Locked nucleic acid modified anti-miRNAs targeted against hsa-miR-29a and 29b specifically reversed the inhibitory effect mediated by cellular miRNAs on the target site. Ectopic expression of the miRNA results in repression of the target Nef protein and reduction of virus levels.


CONCLUSIONS
Our results show that the cellular miRNA hsa-miR29a downregulates the expression of Nef protein and interferes with HIV-1 replication.
Ahluwalia
Jasmine K
JK
Institute of Genomics and Integrative Biology (IGIB) CSIR, Delhi, India. jasmine.ahluwalia@igib.res.in
Khan
Sohrab Zafar
SZ
Soni
Kartik
K
Rawat
Pratima
P
Gupta
Ankit
A
Hariharan
Manoj
M
Scaria
Vinod
V
Lalwani
Mukesh
M
Pillai
Beena
B
Mitra
Debashis
D
Brahmachari
Samir K
SK
D001483:Base Sequence; D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D008969:Molecular Sequence Data; D014779:Virus Replication / Q000187:drug effects*; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics* / Q000378:metabolism*
C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D054311:nef Gene Products, Human Immunodeficiency Virus