The octamer-binding protein Oct-2 represses HSV immediate-early genes in cell lines derived from latently infectable sensory neurons

Abstract

Transcription of herpes simplex virus (HSV) immediate-early (IE) genes does not occur in sensory neurons latently infected with the virus or following infection of neuronal cell lines. In neuronal cell lines this inability results from the weak activity of the viral IE promoters, which is caused by a neuron-specific repressor factor that binds specifically to the TAATGARAT motif in these promoters and to related octamer elements. Cells expressing this repressor contain an additional octamer-binding protein that is absent from permissive cells. We identify this factor as the lymphocyte- and neuron-specific octamer-binding protein Oct-2 and show that Oct-2 mRNA is also present in dorsal root ganglion neurons, the natural site of HSV latency in vivo. Moreover, artificially elevated expression of Oct-2 can repress the IE promoter. The potential role of Oct-2 in the initiation and maintenance of in vivo latent infection with HSV is discussed.

Comparative analysis of genomic HSV vectors for gene delivery to motor neurons following peripheral inoculation in vivo

“…35 Differences in transcription factors could also be responsible for the ability of the vector to establish latency in one particular cell type. 38 Studies using an HSV-1-derived vector containing the LAP1-MMLV-LTR LacZ construct in the gC locus have also reported differences in the efficiency of gene delivery where, following intramuscular inoculation, long-term transgene expression was seen in the DRG 39 but not in motor neurons. 33 The inability to obtain long-term gene delivery with the replication-competent vectors used here is at least partially due to an adaptive immune response.…”

The roles of herpes simplex virus in neuroscience

“…The restriction of viral replication within these cells occurs at the level of HSV a gene expression and appears to be due to the presence of a cellular repressor that binds to the TAATGARAT motif (Kemp and Latchman, 1989;Werstuck et al, 1990). Lillycrop et al (1991) defined the cellular repressor as a neuronal homolog to the Oct-2 transcriptional factor. Oct-2 is related to Oct-1 and has been shown to be capable of binding to the TAATGARAT sequence (Gerster and Roeder, 1988).…”

Quiescent viral genomes in human fibroblasts after infection with herpes simplex virus type 1 Vmw65 mutants

“…It has been suggested that a block to IE transcription, possibly imposed by inhibitory TAATGARAT-binding proteins, is primarily responsible for the abortion of lytic replication and hence the establishment of latency (Roizrnan & Sears, 1987;Kristie & Roizmam 1988;Kemp et al, 1990;Lillycrop et al, 1991Lillycrop et al, , 1994Sears et al, 1991). In support of this hypothesis, in1814 establishes latency after inoculation into mice even though productive infection in neurons is impaired, suggesting that IE gene expression is not required for latency (Steiner et al, 1990;Valyi-Nagy et al, 1991;Ecob-Prince et al, 1993).…”