Article ; Online: Increased neurovirulence and reactivation of the herpes simplex virus type 1 latency-associated transcript (LAT)-negative mutant dLAT2903 with a disrupted LAT miR-H2.
2016 Volume 22, Issue 1, Page(s) 38–49
Abstract: At least six microRNAs (miRNAs) appear to be encoded by the latency-associated transcript (LAT) of herpes simplex virus type 1 (HSV-1). The gene for ICP0, an important immediate early (IE) viral protein, is anti-sense to, and overlaps with, the region of ...
| Abstract | At least six microRNAs (miRNAs) appear to be encoded by the latency-associated transcript (LAT) of herpes simplex virus type 1 (HSV-1). The gene for ICP0, an important immediate early (IE) viral protein, is anti-sense to, and overlaps with, the region of LAT from which miRNA H2 (miR-H2) is derived. We recently reported that a mutant (McK-ΔH2) disrupted for miR-H2 on the wild-type HSV-1 strain McKrae genomic background has increased ICP0 expression, increased neurovirulence, and slightly more rapid reactivation. We report here that HSV-1 mutants deleted for the LAT promoter nonetheless make significant amounts of miR-H2 during lytic tissue culture infection, presumably via readthrough transcription from an upstream promoter. To determine if miR-H2 might also play a role in the HSV-1 latency/reactivation cycle of a LAT-negative mutant, we constructed dLAT-ΔH2, in which miR-H2 is disrupted in dLAT2903 without altering the predicted amino acid sequence of the overlapping ICP0 open reading frame. Similar to McK-ΔH2, dLAT-ΔH2 expressed more ICP0, was more neurovirulent, and had increased reactivation in the mouse TG explant-induced reactivation model of HSV-1 compared with its parental virus. Interestingly, although the increased reactivation of McK-ΔH2 compared with its parental wild-type (wt) virus was subtle and only detected at very early times after explant TG induced reactivation, the increased reactivation of dLAT-ΔH2 compared with its dLAT2903 parental virus appeared more robust and was significantly increased even at late times after induction. These results confirm that miR-H2 plays a role in modulating the HSV-1 reactivation phenotype. |
|---|---|
| MeSH term(s) | Animals ; Cell Line, Tumor ; Disease Models, Animal ; Female ; Gene Expression Regulation, Viral ; Herpes Simplex/pathology ; Herpes Simplex/virology ; Herpesvirus 1, Human/genetics ; Herpesvirus 1, Human/metabolism ; Herpesvirus 1, Human/pathogenicity ; Humans ; Immediate-Early Proteins/genetics ; Immediate-Early Proteins/metabolism ; Mice ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Neurons/pathology ; Neurons/virology ; Promoter Regions, Genetic ; RNA, Viral/genetics ; RNA, Viral/metabolism ; Tissue Culture Techniques ; Trigeminal Ganglion/pathology ; Trigeminal Ganglion/virology ; Ubiquitin-Protein Ligases/genetics ; Ubiquitin-Protein Ligases/metabolism ; Virulence ; Virus Activation/genetics ; Virus Latency/genetics |
| Chemical Substances | Immediate-Early Proteins ; MicroRNAs ; RNA, Viral ; latency associated transcript, herpes simplex virus-1 ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; Vmw110 protein, Human herpesvirus 1 (EC 2.3.2.27) |
| Language | English |
| Publishing date | 2016-02 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 1283265-0 |
| ISSN | 1538-2443 ; 1355-0284 |
| ISSN (online) | 1538-2443 |
| ISSN | 1355-0284 |
| DOI | 10.1007/s13365-015-0362-y |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
Full text online
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
| Zs.A 4426: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG) |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.