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 journalArticle

132 Citations (Scopus)

Abstract

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
JournalVirology
Volume247
Issue number2
DOIs
StatePublished - Aug 1 1998

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Virus Activation
Human Herpesvirus 1
Virus Replication
Virus Diseases
Simplexvirus
Viruses
Immediate-Early Proteins
Ankyrin Repeat
Neutralizing Antibodies
Cell Nucleus
Glycoproteins
Cytoplasm
Transcription Factors
Tumor Necrosis Factor-alpha
Gene Expression
Infection
Proteins

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Herpes simplex virus type 1 induction of persistent NF-κB nuclear translocation increases the efficiency of virus replication. / Patel, Amit; Hanson, Julie; McLean, Tim I.; Olgiate, Jennifer; Hilton, Melissa; Miller, William E.; Bachenheimer, Steven L.

In: Virology, Vol. 247, No. 2, 01.08.1998, p. 212-222.

Research output: Contribution to journalArticle

Patel, Amit ; Hanson, Julie ; McLean, Tim I. ; Olgiate, Jennifer ; Hilton, Melissa ; Miller, William E. ; Bachenheimer, Steven L. / Herpes simplex virus type 1 induction of persistent NF-κB nuclear translocation increases the efficiency of virus replication. In: Virology. 1998 ; Vol. 247, No. 2. pp. 212-222.
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