Scientific Publications by FDA Staff
J Virol 2009 Feb;83(3):1433-42
Novel less-abundant viral microRNAs encoded by herpes simplex virus 2 latency-associated transcript and their roles in regulating ICP34.5 and ICP0 mRNAs.
Tang S, Patel A, Krause PR
We recently identified an acutely and latently expressed viral miRNA, miR-I, encoded by herpes simplex virus 2 (HSV-2) latency-associated transcript (LAT) through small RNA cloning, and two miRNAs encoded by herpes simplex virus 1 (HSV-1) LAT through prediction. We now report the use of high throughput sequencing technology to identify two additional relatively less-abundant viral miRNAs, miR-II and miR-III, encoded by HSV-2 LAT exon 2. miR-II includes two miRNAs, miR-II-5p and miR-II-3p, which are processed from the same miRNA precursor. miR-II and miR-III map antisense to the 5' UTR region of ICP34.5 and to the coding region of ICP0 exon 3, respectively. These novel miRNAs are conserved in different HSV-2 strains and were confirmed by Northern hybridization in infected and transfected cell cultures. All three HSV-2 LAT-encoded miRNAs map to similar genome locations as three out of four identified HSV-1 LAT-encoded miRNAs, but the sequences of these miRNAs are not conserved. The expression of LAT-encoded miRNAs is negatively regulated by ICP4, the major viral trans-activator. We further show that similarly to miR-I, miR-II is able to efficiently silence the expression of ICP34.5, a key viral neurovirulence factor, and miR-III is able to silence the expression of ICP0, a key viral trans-activator. All these data suggest that LAT sequences likely contribute to HSV latency and reactivation through tight control of these LAT-encoded miRNAs and their viral targets.
|Category: Journal Article|
|PubMed ID: #19019961||DOI: 10.1128/JVI.01723-08|
|Includes FDA Authors from Scientific Area(s): Biologics|
|Entry Created: 2011-10-04||Entry Last Modified: 2012-08-29|