Scientific Publications by FDA Staff
J Virol 2011 May;85(9):4501-9
Herpes Simplex Virus-2 miR-H6 is a Novel LAT-associated MicroRNA, but Reduction of its Expression Does not Influence Viral Latency Establishment or Recurrence Phenotype.
Tang S, Bertke AS, Patel A, Margolis TP, Krause PR
The herpes simplex virus 2 (HSV-2) viral miRNA designated miR-H6 is located upstream of the latency-associated transcript (LAT) promoter region, on the strand opposite the LAT. Deletion of the LAT promoter and part of LAT exon 1 abolished HSV-2 miR-H6 expression in acutely and latently infected guinea pig DRG, suggesting that this region is needed both for the expression of LAT-encoded miRNAs and for miR-H6 expression in vivo. Relative to cells infected with a viral rescuant, miR-H6 expression was significantly reduced in cells infected with a mutant HSV-2 virus, NotPolyA, with an insertion of an SV40 polyadenylation signal sequence between the LAT promoter and miR-H6 sequences. In addition, miR-H6 expression, but not LAT or viral DNA, was significantly reduced in both mouse TG and guinea pig DRG latently infected with the NotPolyA mutant. Guinea pigs infected with NotPolyA experienced reduced neurological complications of acute infection, relative to those infected with the rescuant, but the recurrence phenotype of the NotPolyA mutant was similar to its rescuant and wild-type HSV-2, indicating that reduction of miR-H6 expression is not by itself able to alter the wild-type latency establishment and recurrence phenotype. Furthermore, the mutation in NotPolyA did not affect the propensity of wild-type HSV-2 to establish latency in KH10-positive neurons. In contrast to published reports regarding its HSV-1 homolog, HSV-2 miR-H6 did not affect ICP4 expression in transfected or infected cells. We hypothesize that viral miRNAs associated with LAT expression are likely to work collectively, contributing to the phenotype attributed to the LAT.
|Category: Journal Article|
|PubMed ID: #21325410||DOI: 10.1128/JVI.01997-10|
|Includes FDA Authors from Scientific Area(s): Biologics|
|Entry Created: 2011-10-03||Entry Last Modified: 2012-08-29|