Gene array analysis reveals changes in peripheral nervous system gene expression following stimuli that result in reactivation of latent herpes simplex virus type 1: induction of transcription factor Bcl-3.
The earliest events within the peripheral mammalian nervous system that cause herpes simplex virus type 1 (HSV-1) to reactivate from latency are unknown but are highly likely to include altered regulation of cellular transcription factors. Using gene array analysis, we have examined the changes that occur in cellular mRNA levels in mouse trigeminal ganglia following explantation, a stimulus that results in HSV-1 reactivation from latency. We have detected both increased and decreased expression levels of particular cellular transcripts, which include RNAs encoding neuronal factors, transcription factors, and factors involved in the cell cycle. Among the transcription factors that are upregulated is Bcl-3, a coactivator for NFkappaB. We have confirmed these increases in Bcl-3 transcription levels using reverse transcription-PCR and S1 nuclease protection assays. In addition, we have shown Bcl-3 upregulation at the protein level. Importantly, Bcl-3 RNA levels were found to increase specifically in neuronal cells within the trigeminal ganglia. We discuss a potential role for this factor in upregulating ICP0 transcription, which is an important viral event for initiation of HSV-1 reactivation.
Tsavachidou
D
D
The Wistar Institute, Philadelphia, Pennsylvania 19104-4268, USA.
Podrzucki
W
W
Seykora
J
J
Berger
S L
SL
D000818:Animals; D000081242:B-Cell Lymphoma 3 Protein; D015153:Blotting, Western; D005260:Female; D020869:Gene Expression Profiling; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000502:physiology*; D017403:In Situ Hybridization; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D017933:Peripheral Nervous System / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D013997:Time Factors; D014157:Transcription Factors; D015854:Up-Regulation; D014775:Virus Activation; D017735:Virus Latency
D000081242:B-Cell Lymphoma 3 Protein; C000631344:BCL3 protein, human; C000631345:Bcl3 protein, mouse; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D014157:Transcription Factors