Epstein-Barr virus-encoded microRNA miR-BART2 down-regulates the viral DNA polymerase BALF5.
MicroRNAs (miRNAs) have been implicated in sequence-specific cleavage, translational repression or deadenylation of specific target mRNAs resulting in post-transcriptional gene silencing. Epstein-Barr virus (EBV) encodes 23 miRNAs of unknown function. Here we show that the EBV-encoded miRNA miR-BART2 down-regulates the viral DNA polymerase BALF5. MiR-BART2 guides cleavage within the 3'-untranslated region (3'UTR) of BALF5 by virtue of its complete complementarity to its target. Induction of the lytic viral replication cycle results in a reduction of the level of miR-BART2 with a strong concomitant decrease of cleavage of the BALF5 3'UTR. Expression of miR-BART2 down-regulates the activity of a luciferase reporter gene containing the BALF5 3'UTR. Forced expression of miR-BART2 during lytic replication resulted in a 40-50% reduction of the level of BALF5 protein and a 20% reduction of the amount of virus released from EBV-infected cells. Our results are compatible with the notion that EBV-miR-BART2 inhibits transition from latent to lytic viral replication.
Barth
Stephanie
S
Institute of Virology, University of Saarland Medical School, 66424 Homburg, Germany.
Pfuhl
Thorsten
T
Mamiani
Alfredo
A
Ehses
Claudia
C
Roemer
Klaus
K
Kremmer
Elisabeth
E
Jäker
Christoph
C
Höck
Julia
J
Meister
Gunter
G
Grässer
Friedrich A
FA
D020413:3' Untranslated Regions / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D051381:Rats; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication
D020413:3' Untranslated Regions; D004268:DNA-Binding Proteins; D035683:MicroRNAs; D014764:Viral Proteins; D008156:Luciferases; C083202:BALF5 protein, Epstein-barr virus; D004259:DNA-Directed DNA Polymerase