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. 2005 Mar;79(6):3873-7.
doi: 10.1128/JVI.79.6.3873-3877.2005.

Human cytomegalovirus immediate-early 2 gene expression blocks virus-induced beta interferon production

R Travis Taylor  1 , Wade A Bresnahan
Affiliations

Human cytomegalovirus immediate-early 2 gene expression blocks virus-induced beta interferon production

R Travis Taylor et al. J Virol. 2005 Mar.

Abstract

The effect of human cytomegalovirus (HCMV) gene expression on beta interferon (IFN-beta) expression was examined. We demonstrate that the HCMV immediate-early 2 (IE2) gene product IE86 can effectively block the induction of IFN-beta during HCMV infection. IE86 also efficiently blocked the induction of IFN-beta following Sendai virus infection, demonstrating that IE86's ability to block induction of IFN-beta is not limited to HCMV infection, identifying IE2 as an IFN-beta antagonist.

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Figures

FIG. 1.
FIG. 1.
HCMV and IFN-β expression. (A) HCMV replication is inhibited by IFN-β treatment. HFF cells were mock treated or treated with 500 IU of IFN-β/ml. Cells were then infected with HCMV at a multiplicity of 0.1 PFU/cell. After 1 h of incubation, the inoculum was replaced with fresh medium either with or without 500 IU of IFN-β/ml. Virus was harvested 10 days postinfection and quantified by plaque assay on HFF cells. Conditions were mock treatment (black bar), pretreatment alone (horizontally striped bar), posttreatment alone (cross-hatched bar), and continuous treatment (open bar). (B) HFF cells were either mock infected; infected with HCMV, UV-inactivated HCMV, or wild-type HCMV in the presence of 100 μg of cycloheximide (CHX)/ml; or treated with cycloheximide alone. RNA was isolated 6 h posttreatment and analyzed for IFN-β, IE1, and GAPDH transcript by Northern blotting. (C) HFF cells were infected at a multiplicity of 5 PFU/cell with either HCMV or UV-inactivated HCMV. RNA was harvested at various times postinfection and assayed for IFN-β, IE2, and GAPDH by Northern blotting. (D) Supernatants from cells infected with either wild-type HCMV (open bars) orUV-inactivated HCMV (black bars) were harvested and assayed for IFN-β secretion by ELISA. Data represent the averages of two independent experiments.
FIG. 2.
FIG. 2.
Expression of IE86 blocks the induction of IFN-β during HCMV infection. (A) HFF cells were transduced with replication-defective adenoviruses expressing IE1, IE2, pp65, pp71, or GFP for 24 h. Transduced cells were then infected with UV-HCMV at a multiplicity of 5 PFU/cell. RNA was harvested 6 h postinfection with UV-HCMV and analyzed for IFN-β and GAPDH transcript. Expression of IE72, IE86, pp71, pp65, and GFP expressed from the adenoviruses is also shown. (B) Supernatants from infected samples as described for panel A were assayed for IFN-β secretion by ELISA. Data represent the averages of two independent experiments. WT, wild type. (C) HFF cells were transduced with replication-defective adenoviruses expressing either IE2 or GFP for 24 h. Transduced cells were then infected with HCMV in the presence of 100 μg of cycloheximide (CHX)/ml or treated with CHX alone. RNA was harvested 6 h postinfection and assayed for IFN-β and GAPDH by Northern blotting.
FIG. 3.
FIG. 3.
IE86 blocks the induction of IFN-β expression following Sendai virus infection. (A) HFF cells were either mock infected or infected with HCMV at a multiplicity of 5 PFU/cell. Six hours postinfection the cells were superinfected with Sendai virus (100 hemagglutinin units/ml). RNA was isolated 16 h after Sendai virus infection and assayed for IFN-β, GAPDH, and Sendai virus N transcript by Northern blotting. (B) Supernatants from infected samples described for panel A were assayed for IFN-β secretion by ELISA. Data represent the averages of two independent experiments. WT, wild type; SV, Sendai virus. (C) HFF cells were either mock transduced or transduced with replication-defective adenoviruses for 24 h that express either IE2 or GFP. Transduced cells were then infected with Sendai virus. RNA was isolated 6 h post-Sendai virus infection and assayed for IFN-β, GAPDH, and Sendai virus N transcript by Northern blotting. (D) Supernatants from infected samples described for panel C were assayed for secretion of IFN-β by ELISA. Data represent the averages of two independent experiments.
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