Regulation of stress associated protein kinase signaling pathways and apoptosis by herpes simplex virus Type 1 infected cell protein 27.

Regulation of stress associated protein kinase signaling pathways and apoptosis by herpes simplex virus Type 1 infected cell protein 27.

The accumulation of cellular transcripts from cells infected with herpes simplex virus 1 (HSV-1) as measured with the aid of Affymetrix microchips has been reported elsewhere. The synthetic corticosteroid dexamethasone induces certain cellular transcription factors in murine and bovine trigeminal ganglionic neurons. Three dexamethasone-induced transcription factors, Krüppel-like factor 15, Slug, and SPDEF, stimulated the herpes simplex virus type 1-infected cell protein 0 (ICP0) promoter more than 150-fold. To examine the direct functions of ICP27, we engineered stable HeLa cell lines that inducibly express ICP27. These transcripts reach peak levels between 3 and 7 h after infection and decrease thereafter. Abundant viral protein expression and infectious virus are not readily detected during latency, in contrast to the expression of the virus-encoded latency-associated transcript that occurs in latently infected sensory neurons (1–3). The ability of herpes simplex virus 1 (HSV-1) to reactivate from latency is crucial for virus transmission and recurrent disease.

Regulation of stress associated protein kinase signaling pathways and apoptosis by herpes simplex virus Type 1 infected cell protein 27.
However, it is likely that additional downstream ICP27-dependent viral factors inhibit apoptosis during HSV-1 infection. Neither of these RNAs could translate the authentic IEX-1 protein. With respect to reactivation from latency, there are at least two important unresolved issues: (i) which viral genes might be involved in the initiation of reactivation and (ii) whether the cascade of viral gene expression during reactivation is the same as productive infection of cultured cells (i.e., immediate early [IE] to early [E] to late [L]). Recent studies have suggested that VP16, a late transcript, stimulates reactivation from latency (6, 7), presumably because VP16 stimulates IE gene expression. We demonstrate that the HSV-1 protein UL37 is expressed in an ICP27/JNK signaling-dependent manner and is capable of activating NF-B. 27. Finally, viral gene expression is reported to be initially disorganized during explant-induced reactivation from latency (5, 18).

Regardless of whether VP16 or ICP0 is involved or required for reactivation from latency, it is reasonable to predict that stimulus-specific cellular transcription factors may stimulate viral gene expression during the early stages of reactivation. During the course of these studies, we also observed that ICP27 expression activates elements of the cellular integrated stress response and the endoplasmic reticulum stress pathways leading to eIF2α phosphorylation and IRE1 activation, respectively. The cellular response to ER stress induced by ICP27 could provide a mechanism for induction of SAPK signaling. A subset of these cellular genes consists of transcription factors (Fig. One of the highly induced transcription factors, promyelocytic leukemia zinc finger (PLZF), stimulated BHV-1 productive infection more than 20-fold. (2010). Regulation of stress associated protein kinase signaling pathways and apoptosis by herpes simplex virus Type 1 infected cell protein 27..

In contrast, PLZF and SPDEF (SAM pointed domain containing Ets transcription factor) stimulated the L BHV-1 gC promoter to a higher degree than the bICP0 E promoter and the IE transcription unit 1 promoter.

You may also like