Expression of Krüppel-like factor 15 (KLF15), a stress-induced transcription factor, is
induced during bovine herpesvirus 1 (BoHV-1) reactivation from latency, and KLF15 stimulates
BoHV-1 replication. Transient transfection studies revealed that KLF15 and glucocorticoid receptor
(GR) cooperatively transactivate the BoHV-1-immediate-early transcription unit 1 (IEtu1), herpes
simplex virus type 1 (HSV-1) infected cell protein 0 (ICP0), and ICP4 promoters. The IEtu1 promoter
drives expression of bICP0 and bICP4, two key BoHV-1 transcriptional regulatory proteins. Based
on these studies, we hypothesized infection is a stressful stimulus that increases KLF15 expression
and enhances productive infection. New studies demonstrated that silencing KLF15 impaired HSV-1
productive infection, and KLF15 steady-state protein levels were increased at late stages of productive
infection. KLF15 was primarily localized to the nucleus following infection of cultured cells with
HSV-1, but not BoHV-1. When cells were transfected with a KLF15 promoter construct and then
infected with HSV-1, promoter activity was significantly increased. The ICP0 gene, and to a lesser
extent, bICP0 transactivated the KLF15 promoter in the absence of other viral proteins. In contrast,
BoHV-1 or HSV-1 encoded VP16 had no effect on KLF15 promoter activity. Collectively, these studies
revealed that HSV-1 and BoHV-1 productive infection increased KLF15 steady-state protein levels,
which correlated with increased virus production.