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01.04.2015

A herpes simplex virus type 1 mutant disrupted for microRNA H2 with increased neurovirulence and rate of reactivation

verfasst von: Xianzhi Jiang, Don Brown, Nelson Osorio, Chinhui Hsiang, Lily Li, Lucas Chan, Lbachir BenMohamed, Steven L. Wechsler

Erschienen in: Journal of NeuroVirology | Ausgabe 2/2015

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Abstract

The herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) encodes several microRNAs. One of these, miR-H2, overlaps and is antisense to the ICP0 gene and appears to decrease expression of the ICP0 protein. To determine if miR-H2 plays a role in the HSV-1 latency-reactivation cycle, we constructed a mutant, McK-ΔH2, in which this microRNA has been disrupted without altering the predicted amino acid sequence of ICP0. McK-ΔH2 produced increased amounts of ICP0. Although replication of McK-ΔH2 was similar to that of its wild-type (wt) McKrae parental virus in RS cells and mouse eyes, McK-ΔH2 was more neurovirulent in Swiss-Webster mice than McKrae based on the percent of mice that died from herpes encephalitis following ocular infection. In addition, using a mouse trigeminal ganglia (TG) explant model of induced reactivation, we show here for the first time that miR-H2 appears to play a role in modulating HSV-1 reactivation. Although the percent of TG from which virus reactivated by day 10 after explant was similar for McK-ΔH2, wt McKrae, and the marker-rescued virus McK-ΔH2Res, at earlier times, significantly more reactivation was seen with McK-ΔH2. Our results suggest that in the context of the virus, miR-H2 downregulates ICP0 and this moderates both HSV-1 neurovirulence and reactivation.

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Titel: A herpes simplex virus type 1 mutant disrupted for microRNA H2 with increased neurovirulence and rate of reactivation
verfasst von: Xianzhi Jiang
Don Brown
Nelson Osorio
Chinhui Hsiang
Lily Li
Lucas Chan
Lbachir BenMohamed
Steven L. Wechsler
Publikationsdatum: 01.04.2015
Verlag: Springer US
Erschienen in: Journal of NeuroVirology / Ausgabe 2/2015
Print ISSN: 1355-0284
Elektronische ISSN: 1538-2443
DOI: https://doi.org/10.1007/s13365-015-0319-1

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