Herpes simplex virus type 1 induction of persistent NF-κB nuclear translocation increases the efficiency of virus replication

Amit Patel, Julie Hanson, Tim I. McLean, Jennifer Olgiate, Melissa Hilton, William E. Miller, Steven L. Bachenheimer

Research output: Contribution to journalArticlepeer-review

143 Scopus citations


The latent form of the dimeric transcription factor NF-κB is sequestered in the cytoplasm by proteins containing ankyrin repeats, such as IκBα and β, or by the p105 precursor form of the NF-κB p50 subunit. Tumor necrosis factor α or virus infection can cause targeted destruction of IκB and nuclear translocation of NF-κB. Following translocation, NF-κB mediates immune, inflammatory, or anti-apoptotic responses. Here we present evidence that beginning at around 6 h postinfection, herpes simplex virus (HSV) induces a persistent translocation of NF-κB into the nucleus of C33 cells, coincident with loss of both IκBα and IκBβ. Translocation failed to occur when infecting virus was preincubated with neutralizing antibody to viral envelope glycoproteins gD or gH, thus preventing entry, or when cells were infected with viruses expressing mutated forms of immediate-early regulatory proteins ICP4 or ICP27. Surprisingly, no increase in the trans-activation function of NF-κB, as assayed by transient expression of CAT, was detected following HSV infection. The significance of NF-κB nuclear translocation for virus replication was demonstrated by an 80-90% reduction in virus yield following infection of C33 cells expressing a constitutive repressor form of IκBα. Models that reconcile nuclear translocation of NF-κB with the inability to detect NF-κB-dependent gene expression are discussed.

Original languageEnglish (US)
Pages (from-to)212-222
Number of pages11
Issue number2
StatePublished - Aug 1 1998

Bibliographical note

Funding Information:
Several colleagues contributed generously to these studies: Albert Baldwin, Eng-Shang Huang, and Andrew Yurochko for NF-κB-dependent CAT reporter plasmids; Patricia Spear for virus neutralizing antibodies; Roz Eisenberg, Gary Cohen, Ken Powell, and Le-nore Periera for antibodies used in Western blot analyses; and Bernard Roizman, David Knipe, Stephen Rice, Neal DeLuca, Priscilla Schaffer, and David Leib for viral mutants. Albert Baldwin, Jeanette Cheshire, Kate Ryman, and Andrew Yurochko provided invaluable advice. J.H. was supported by an NSF Research Experience for Undergraduates Award 96–05149; T.I.M. was supported by NIH NIGMS T32 GM 07092. W.E.M. was supported in part by predoctoral NIH National Service Award AI07519–02. These studies were supported by PHS Program Project Grant CA 19014 to S.L.B.


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