NF-κB Is Required for Apoptosis Prevention during Herpes Simplex Virus Type 1 Infection

• DOI: 10.1128/jvi.77.13.7261-7280.2003
• Publication Date: 2003-06-13T00:18:39Z
• Authors: Margot L. Goodkin; Adrian T. Ting; John A. Blaho
• Keywords: Staurosporine

ABSTRACT Wild-type herpes simplex virus type 1 (HSV-1) infection triggers apoptosis in human cells. The subsequent synthesis of infected cell proteins between 3 and 6 h postinfection (hpi) acts to block this process from killing the factors produced during window also prevent death induced by environmental staurosporine or sorbitol (M. Aubert, J. O'Toole, A. Blaho, Virol. 73:10359-10370, 1999). We now report that (i) prevention window, HSV-1(F) inhibited tumor necrosis factor alpha (TNF-α) plus cycloheximide (CHX) treatment. While deciphering mechanism inhibition, we observed (ii) transcription NF-κB translocated cytoplasm into nuclei cells, (iii) migration initiated at hpi. (iv) complete inhibition protein hpi addition CHX precluded translocation, while additions later did not elicit effect. This result confirms is required for nuclear import NF-κB. (v) detection correlated with ability HSV-1(F), HSV-1(KOS1.1), HSV-1(R7032), a replication-competent recombinant containing deletion gene encoding gE glycoprotein, apoptosis. (vi) bind its κB DNA recognition site remained cytoplasmic cells actively undergoing following HSV-1(vBSΔ27), key regulatory ICP27 deleted. (vii) Prestimulation phorbol ester prevented HSV-1(vBSΔ27)-induced (viii) Retention pharmacological antagonist release IκBα led an increase processing infection. (ix) A novel HEp-2 clonal line, termed IκBαDN, was generated which expresses dominant-negative form IκBα. Treatment IκBαDN TNF-α absence resulted apoptotic due inability become activated these Finally, (x) HSV-1(KOS1.1) apoptosis, demonstrating (xi) translocation (the window) necessary wild-type HSV-1-infected