A Mutation in the Latency-Related Gene of Bovine Herpesvirus 1 Disrupts the Latency Reactivation Cycle in Calves

Inman, Melissa; Lovato, Luciane Teresinha; Doster, Alan R.; Jones, Clinton

doi:10.1128/jvi.76.13.6771-6779.2002

Cited by 84 publications

(160 citation statements)

References 54 publications

(55 reference statements)

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“…The LRT mutants were shed at similar rates from the nasal cavity during the primary infection [80,158]. In latently infected neurons, reduced levels of viral DNA were detected [81] but higher levels of apoptosis occurred in trigeminal ganglion at the end of the acute infection [118]. The BoHV-1 LRT mutants were not re-excreted following a reactivation treatment with dexamethasone, which induced reactivation and re-excretion in all calves infected by either wild-type or LRT rescued virus [81].…”

Section: Latency and Reactivationmentioning

confidence: 94%

“…In latently infected neurons, reduced levels of viral DNA were detected [81] but higher levels of apoptosis occurred in trigeminal ganglion at the end of the acute infection [118]. The BoHV-1 LRT mutants were not re-excreted following a reactivation treatment with dexamethasone, which induced reactivation and re-excretion in all calves infected by either wild-type or LRT rescued virus [81]. Moreover a chimeric HSV-1 mutant where the BoHV-1 LR gene replaces the deleted Latency Associated Transcript locus of HSV-1 presents a high level of spontaneous reactivation in the rabbit eye model [159].…”

Section: Latency and Reactivationmentioning

confidence: 99%

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Bovine herpesvirus 1 infection and infectious bovine rhinotracheitis

et al. 2007

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-Bovine herpesvirus 1 (BoHV-1), classified as an alphaherpesvirus, is a major pathogen of cattle. Primary infection is accompanied by various clinical manifestations such as infectious bovine rhinotracheitis, abortion, infectious pustular vulvovaginitis, and systemic infection in neonates. When animals survive, a life-long latent infection is established in nervous sensory ganglia. Several reactivation stimuli can lead to viral re-excretion, which is responsible for the maintenance of BoHV-1 within a cattle herd. This paper focuses on an updated pathogenesis based on a molecular characterization of BoHV-1 and the description of the virus cycle. Special emphasis is accorded to the impact of the latency and reactivation cycle on the epidemiology and the control of BoHV-1. Several European countries have initiated BoHV-1 eradication schemes because of the significant losses incurred by disease and trading restrictions. The vaccines used against BoHV-1 are described in this context where the differentiation of infected from vaccinated animals is of critical importance to achieve BoHV-1 eradication.

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Section: Latency and Reactivationmentioning

confidence: 94%

Section: Latency and Reactivationmentioning

confidence: 99%

Bovine herpesvirus 1 infection and infectious bovine rhinotracheitis

et al. 2007

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“…The animal ID # was used to identify the respective calves. The clinical data and virus titres obtained from these calves following infection were previously described (Inman et al, 2001 andInman et al, 2002). +, Transcript was detected; 2, transcript was not detected; ND, not determined.…”

Section: Discussionmentioning

confidence: 99%

Premature expression of the latency-related RNA encoded by bovine herpesvirus type 1 correlates with higher levels of beta interferon RNA expression in productively infected cells

Pérez

Meyer

Saira

et al. 2008

Journal of General Virology

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Bovine herpesvirus type 1 (BHV-1) is an important pathogen that can initiate bovine respiratory disease complex. Like other members of the subfamily Alphaherpesvirinae, BHV-1 establishes latency in sensory neurons. The latency-related (LR) gene expresses a family of alternatively spliced transcripts in infected sensory neurons that have the potential to encode several LR proteins. An LR mutant virus that contains three stop codons near the 59 terminus of the first open reading frame in the LR gene does not express two LR proteins or reactivate from latency. In addition, the LR mutant virus induces higher levels of apoptosis in trigeminal ganglionic neurons and grows less efficiently in certain tissues of infected calves. In spite of the reduced pathogenesis, the LR mutant virus, wild-type BHV-1 and the LR rescued virus exhibit identical growth properties in cultured bovine cells. In this study, we demonstrated that during early phases of productive infection the LR mutant virus expressed higher levels of LR-RNA relative to the LR rescued virus or wt BHV-1. Bovine kidney cells infected with the LR mutant virus also induced higher levels of beta interferon RNA and interferon response genes. These results suggest that inappropriate expression of LR-RNA, in the absence of LR protein expression, may influence the latency-reactivation cycle and pathogenic potential of BHV-1.

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“…Reactivation from latency can occur after stress or corticosteroid treatment, which mimics stress (30, 34). Dexamethasone (DEX), a synthetic corticosteroid, reproducibly induces expression of BoHV-1 lytic cycle genes and reactivation from latency in calves or rabbits (15,(17)(18)(19)(20)30).During productive infection of cultured cells, viral gene expression is temporally regulated in three distinct phases: the immediate-early (IE), early (E), and late (L) phases (reviewed in references 17 and 18). IE gene expression is stimulated by a virion component, bTIF, which interacts with a cellular transcription factor (Oct-1) to transactivate IE gene expression (22,23).…”

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confidence: 99%

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confidence: 99%

Productive Infection and bICP0 Early Promoter Activity of Bovine Herpesvirus 1 Are Stimulated by E2F1

Workman

Jones

2010

J Virol

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Bovine herpesvirus 1 (BoHV-1) is an important viral pathogen of cattle. Like other members of the subfamily Alphaherpesvirinae, BoHV-1 establishes latency in sensory neurons and has the potential to reactivate from latency. Dexamethasone (DEX) treatment of latently infected calves or rabbits consistently leads to reactivation from latency. The BoHV-1 transcript encoding the infected cell protein 0 (bICP0) is consistently detected during reactivation from latency, in part because the bICP0 early promoter is activated by DEX. During DEX-induced reactivation from latency, cyclin expression is stimulated in infected sensory neurons. Cyclindependent kinase activity phosphorylates Rb (retinoblastoma tumor suppressor gene product) family proteins and consequently releases the E2F family of transcription factors, suggesting that E2F family members stimulate productive infection and/or reactivation from latency. In this study, we provide evidence that repression of E2F1 by a specific small interfering RNA (siRNA) reduced productive infection approximately 5-fold. E2F1 or E2F2 stimulated bICP0 early promoter activity at least 100-fold in transient transfection assays. Two E2F-responsive regions (ERR) were identified within the early promoter, with one adjacent to the TATA box (ERR1) and one approximately 600 bp upstream from the TATA box (ERR2). Mobility shift assays suggested that E2F interacts with ERR1 and ERR2. E2F1 protein levels were increased at late times after infection, which correlated with enhanced binding to a consensus E2F binding site, ERR1, or ERR2. Collectively, these studies suggest that E2F1 stimulates productive infection and bICP0 early promoter activity, in part because E2F family members interact with ERR1 and ERR2.Bovine herpesvirus 1 (BoHV-1) is a significant viral pathogen of cattle that can cause conjunctivitis, rhinotracheitis, pneumonia, genital disorders, or abortions. BoHV-1 also initiates shipping fever, a potentially fatal polymicrobial disease (37). Like other members of the Alphaherpesvirinae subfamily, BoHV-1 establishes lifelong latency in trigeminal ganglionic neurons following acute replication in mucosal epithelium. Reactivation from latency occurs periodically, resulting in virus shedding and spread to susceptible cattle. Reactivation from latency can occur after stress or corticosteroid treatment, which mimics stress (30, 34). Dexamethasone (DEX), a synthetic corticosteroid, reproducibly induces expression of BoHV-1 lytic cycle genes and reactivation from latency in calves or rabbits (15,(17)(18)(19)(20)30).During productive infection of cultured cells, viral gene expression is temporally regulated in three distinct phases: the immediate-early (IE), early (E), and late (L) phases (reviewed in references 17 and 18). IE gene expression is stimulated by a virion component, bTIF, which interacts with a cellular transcription factor (Oct-1) to transactivate IE gene expression (22,23). Two IE transcription units exist, namely, IE transcription unit 1 (IEtu1) and IEtu2 (44-46). IEtu1 enc...

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A Mutation in the Latency-Related Gene of Bovine Herpesvirus 1 Disrupts the Latency Reactivation Cycle in Calves

Cited by 84 publications

References 54 publications

Bovine herpesvirus 1 infection and infectious bovine rhinotracheitis

Bovine herpesvirus 1 infection and infectious bovine rhinotracheitis

Premature expression of the latency-related RNA encoded by bovine herpesvirus type 1 correlates with higher levels of beta interferon RNA expression in productively infected cells

Productive Infection and bICP0 Early Promoter Activity of Bovine Herpesvirus 1 Are Stimulated by E2F1

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