Inhibition of herpes simplex virus infection by ectopic expression of neuronal splice variants of the Oct-2 transcription factor.
Herpes simplex virus (HSV) is capable of lytic replication in most cells, such replication in epithelial cells resulting in the mucocutaneous lesions observed following in vivo infection. In addition however, the virus also establishes asymptomatic latent infections in sensory neurons which serve as a reservoir for further cycles of peripheral lytic infections. These latent infections are dependent upon the inhibition of viral immediate-early (IE) gene expression via the octamer-related TAATGARAT motif in the IE promoters resulting in the failure of the viral lytic cycle. Here we show that the ectopic expression of neuronal isoforms of the octamer/TAATGARAT-binding transcription factor Oct-2 in permissive BHK cells represses IE gene expression following HSV infection and inhibits the viral lytic cycle whereas the B lymphocyte isoform of Oct-2 does not have this effect. These results suggest that the neuronal isoforms of Oct-2 play a critical role in rendering neuronal cells non-permissive for the viral lytic cycle thereby allowing the establishment of latent infection. Moreover, this is the first time that the ectopic expression of a cellular transcription factor has been shown to inhibit infection with any virus, raising the possibility of therapeutically inhibiting lytic viral infections by inducing such ectopic expression.
Lillycrop
K A
KA
Department of Molecular Pathology, University College London Medical School, UK.
Howard
M K
MK
Estridge
J K
JK
Latchman
D S
DS
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D017874:Immediate-Early Proteins / Q000235:genetics; D009474:Neurons / Q000378:metabolism; D012326:RNA Splicing; D018139:Simplexvirus / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors; D014162:Transfection; D014779:Virus Replication
D004268:DNA-Binding Proteins; D017874:Immediate-Early Proteins; D014157:Transcription Factors