title: Effects of interferon on immediate-early mRNA and protein levels in sensory neuronal cells infected with herpes simplex virus type 1 or pseudorabies virus.
abstract: Most alphaherpesviruses are able to establish latency in sensory neurons and reactivate upon specific stimuli to cause recurrent symptoms. We have previously shown that interferon (IFN) is capable of inducing a quiescent HSV-1 and PRV infection that strongly resembles in vivo latency in primary cultures of TG neurons. This IFN-induced latency-like quiescence was found to correlate with suppression of the immediate-early protein ICP4 in HSV-1 and its ortholog IE180 in PRV. Here, we mechanistically investigated the IFN-mediated suppression of ICP4 and IE180 in sensory neuronal cells. RT-qPCR showed that mRNA levels of either HSV ICP4 or PRV IE180 at 4 hpi were mildly but not significantly different in IFN-treated samples versus control samples, whereas a strong reduction was observed at 8 hpi and 12 hpi. However, at 4 hpi, HSV ICP4 but not PRV IE180 protein expression was already markedly reduced in IFN-treated samples. In line with this difference in IFN-mediated suppression of HSV ICP4 versus PRV IE180 protein levels, we found that IFN resulted in an increase in phosphorylation of the translation initiation factor eIF2α in HSV-infected but not in PRV-infected cells. The latter finding indicates that PRV efficiently circumvents IFN-mediated translation inhibition by interfering with phosphorylation of eIF2α.
authors.affiliation: Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.
authors.forename: Nina
authors.initials: N
authors.lastname: Van Opdenbosch
authors.forename: Nick
authors.initials: N
authors.lastname: De Regge
authors.forename: Mario
authors.initials: M
authors.lastname: Van Poucke
authors.forename: Luc
authors.initials: L
authors.lastname: Peelman
authors.forename: Herman W
authors.initials: HW
authors.lastname: Favoreel
mesh_terms: D000818:Animals; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D006561:Herpes Simplex / Q000378:metabolism / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000502:physiology*; D011558:Herpesvirus 1, Suid / Q000235:genetics / Q000502:physiology*; D017874:Immediate-Early Proteins / Q000235:genetics* / Q000378:metabolism; D007372:Interferons / Q000378:metabolism*; D010766:Phosphorylation; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011984:Sensory Receptor Cells / Q000821:virology*; D017735:Virus Latency
chemical_list: D015852:Eukaryotic Initiation Factor-2; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; C048925:herpes simplex virus, type 1 protein ICP4; D007372:Interferons