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A protein encoded by the bovine herpesvirus 1 latency-related gene interacts with specific cellular regulatory proteins, including CCAAT enhancer binding protein alpha.

ABSTRACT: Following acute infection, bovine herpesvirus 1 establishes latency in sensory neurons of trigeminal ganglia (TG). Reactivation from latency occurs periodically, resulting in the shedding of infectious virus. The latency-related (LR) RNA is abundantly expressed in TG of latently infected calves, and the expression of LR proteins is necessary for dexamethasone-induced reactivation from latency. Previously published studies also identified an alternatively spliced LR transcript which is abundantly expressed in TG at 7 days after infection and has the potential to encode a novel LR fusion protein. Seven days after infection is when extensive viral gene expression is extinguished in TG and latency is established, suggesting that LR gene products influence the establishment of latency. In this study, we used a bacterial two-hybrid assay to identify cellular proteins that interact with the novel LR fusion protein. The LR fusion protein interacts with two proteins that can induce apoptosis (Bid and Cdc42) and with CCAAT enhancer binding protein alpha (C/EBP-alpha). Additional studies confirmed that the LR fusion protein interacts with human or insect C/EBP-alpha. C/EBP-alpha protein expression is induced in TG neurons of infected calves and after dexamethasone-induced reactivation from latency. Wild-type C/EBP-alpha, but not a DNA binding mutant of C/EBP-alpha, enhances plaque formation in bovine cells. We hypothesize that interactions between the LR fusion protein and C/EBP-alpha promote the establishment of latency.

SUBMITTER: Meyer F

PROVIDER: S-EPMC1797275 | biostudies-literature | 2007 Jan

REPOSITORIES: biostudies-literature

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A protein encoded by the bovine herpesvirus 1 latency-related gene interacts with specific cellular regulatory proteins, including CCAAT enhancer binding protein alpha.

Meyer Florencia F Perez Sandra S Geiser Vicki V Sintek Mark M Inman Melissa M Jones Clinton C

Journal of virology 20060920 1

Following acute infection, bovine herpesvirus 1 establishes latency in sensory neurons of trigeminal ganglia (TG). Reactivation from latency occurs periodically, resulting in the shedding of infectious virus. The latency-related (LR) RNA is abundantly expressed in TG of latently infected calves, and the expression of LR proteins is necessary for dexamethasone-induced reactivation from latency. Previously published studies also identified an alternatively spliced LR transcript which is abundantly ...[more]

PMID: 16987965

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Project description:UnlabelledThe UL47 gene product, VP8, is the most abundant tegument protein of bovine herpesvirus 1 (BoHV-1). Previously, we demonstrated that a UL47-deleted BoHV-1 mutant (BoHV1-ΔUL47) exhibits 100-fold-reduced virulence in vitro and is avirulent in vivo In this study, we demonstrated that VP8 expression or BoHV-1 infection inhibits interferon beta (IFN-β) signaling by using an IFN-α/β-responsive plasmid in a luciferase assay. As transducer and activator of transcription (STAT) is an essential component in the IFN-signaling pathways, the effect of VP8 on STAT was investigated. An interaction between VP8 and STAT1 was established by coimmunoprecipitation assays in both VP8-transfected and BoHV-1-infected cells. Two domains of VP8, amino acids 259 to 482 and 632 to 686, were found to be responsible for its interaction with STAT1. The expression of VP8 did not induce STAT1 ubiquitination or degradation. Moreover, VP8 did not reduce STAT1 tyrosine phosphorylation to downregulate IFN-β signaling. However, the expression of VP8 or a version of VP8 (amino acids 219 to 741) that contains the STAT1-interacting domains but not the nuclear localization signal prevented nuclear accumulation of STAT1. Inhibition of nuclear accumulation of STAT1 also occurred during BoHV-1 infection, while nuclear translocation of STAT1 was observed in BoHV1-ΔUL47-infected cells. During BoHV-1 infection, VP8 was detected in the cytoplasm at 2 h postinfection without any de novo protein synthesis, at which time STAT1 was already retained in the cytoplasm. These results suggest that viral VP8 downregulates IFN-β signaling early during infection, thus playing a role in overcoming the antiviral response of BoHV-1-infected cells.ImportanceSince VP8 is the most abundant protein in BoHV-1 virions and thus may be released in large amounts into the host cell immediately upon infection, we proposed that it might have a function in the establishment of conditions suitable for viral replication. Indeed, while nonessential in vitro, it is critical for BoHV-1 replication in vivo In this study, we determined that VP8 plays a role in downregulation of the antiviral host response by inhibiting IFN-β signaling. VP8 interacted with and prevented nuclear accumulation of STAT1 at 2 h postinfection in the absence of de novo viral protein synthesis. Two domains of VP8, amino acids 259 to 482 and 632 to 686, were found to be responsible for this interaction. These results provide a new functional role for VP8 in BoHV-1 infection and a potential explanation for the lack of viral replication of the UL47 deletion mutant in cattle.

Dataset Information

A protein encoded by the bovine herpesvirus 1 latency-related gene interacts with specific cellular regulatory proteins, including CCAAT enhancer binding protein alpha.

Publications

A protein encoded by the bovine herpesvirus 1 latency-related gene interacts with specific cellular regulatory proteins, including CCAAT enhancer binding protein alpha.

Similar Datasets

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