Small non-coding RNAs encoded within the herpes simplex virus type 1 latency associated transcript (LAT) cooperate with the retinoic acid inducible gene I (RIG-I) to induce beta-interferon promoter activity and promote cell survival.

Abstract

The herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) is abundantly expressed in latently infected trigeminal ganglionic sensory neurons. Expression of the first 1.5 kb of LAT coding sequences restores wild type reactivation to a LAT null HSV-1 mutant. The anti-apoptosis functions of the first 1.5 kb of LAT coding sequences are important for wild type levels of reactivation from latency. Two small non-coding RNAs (sncRNAs) contained within the first 1.5 kb of LAT coding sequences are expressed in trigeminal ganglia of latently infected mice, they cooperate to inhibit apoptosis, and reduce the efficiency of productive infection. In this study, we demonstrated that LAT sncRNA1 cooperates with the RNA sensor, retinoic acid inducible gene I (RIG-I), to stimulate IFN-β promoter activity and NF-κB dependent transcription in human or mouse cells. LAT sncRNA2 stimulated RIG-I induction of NF-κB dependent transcription in mouse neuroblastoma cells (Neuro-2A) but not human 293 cells. Since it is well established that NF-κB interferes with apoptosis, we tested whether the sncRNAs cooperated with RIG-I to inhibit apoptosis. In Neuro-2A cells, both sncRNAs cooperated with RIG-I to inhibit cold-shock induced apoptosis. Double stranded RNA (PolyI:C) stimulates RIG-I dependent signaling; but enhanced cold-shock induced apoptosis. PolyI:C, but not LAT sncRNAs, interfered with protein synthesis when cotransfected with RIG-I, which correlated with increased levels of cold-shock induced apoptosis. LAT sncRNA1 appeared to interact with RIG-I in transiently transfected cells suggesting this interaction stimulates RIG-I.

• Authors: Leticia Frizzo da Silva, Clinton Jones
• Journal: Virus research (Virus Res) Vol. 175 Issue 2 Pg. 101-9 (Aug 2013) ISSN: 1872-7492 [Electronic] Netherlands
• PMID: 23648811 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• MicroRNAs
• RNA, Small Untranslated
• RNA, Viral
• Receptors, Immunologic
• latency associated transcript, herpes simplex virus-1
• Interferon-beta
• DDX58 protein, human
• Ddx58 protein, mouse
• DEAD Box Protein 58
• DEAD-box RNA Helicases

Topics

• Animals
• Cell Line
• Cell Survival
• DEAD Box Protein 58
• DEAD-box RNA Helicases (genetics, metabolism)
• Gene Expression Regulation
• Herpesvirus 1, Human (genetics, physiology)
• Host-Pathogen Interactions
• Humans
• Interferon-beta (biosynthesis)
• Mice
• MicroRNAs (genetics)
• Promoter Regions, Genetic
• RNA, Small Untranslated (genetics, metabolism)
• RNA, Viral (genetics, metabolism)
• Receptors, Immunologic