Two MicroRNAs Encoded within the Bovine Herpesvirus 1 Latency-Related Gene Promote Cell Survival by Interacting with RIG-I and Stimulating NF-κB-Dependent Transcription and Beta Interferon Signaling Pathways

Silva, Leticia Frizzo da; Jones, Clinton

doi:10.1128/jvi.06550-11

Cited by 17 publications

(16 citation statements)

References 91 publications

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“…Thus, in our model, we showed that (i) the sensing of BTV is dependent on RLRs that are able to trigger an efficient response to the viral infection and (i) this mechanism is conserved between humans and cattle. The latter statement was recently confirmed by Silva et al, who showed that a constitutively active form of human RIG-I could trigger the activation of the IFN-␤ promoter in bovine testicle cells (59). Moreover, RIG-I and MDA5 show about 80% amino acid sequence identity between humans and bovines, suggesting that they have conserved properties across these species.…”

Section: Discussionmentioning

confidence: 69%

Sensing and Control of Bluetongue Virus Infection in Epithelial Cells via RIG-I and MDA5 Helicases

Chauveau

Doceul

Lara

et al. 2012

J Virol

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Bluetongue virus (BTV), an arthropod-borne member of the Reoviridae family, is a double-stranded RNA virus that causes an economically important livestock disease that has spread across Europe in recent decades. Production of type I interferon (alpha/beta interferon [IFN-␣/␤]) has been reported in vivo and in vitro upon BTV infection. However, the cellular sensors and signaling pathways involved in this process remain unknown. Here we studied the mechanisms responsible for the production of IFN-␤ in response to BTV serotype 8. Upon BTV infection of A549 cells, expression of IFN-␤ and other proinflammatory cytokines was strongly induced at both the protein and mRNA levels. This response appeared to be dependent on virus replication, since exposure to UV-inactivated virus failed to induce IFN-␤. We also demonstrated that BTV infection activated the transcription factors IFN regulatory factor 3 and nuclear factor B. We investigated the role of several pattern recognition receptors in this response and showed that expression of IFN-␤ was greatly reduced after small-interfering-RNA-mediated knockdown of the RNA helicase encoded by retinoic acid-inducible gene I (RIG-I) or melanoma differentiation-associated gene 5 (MDA5). In contrast, silencing of MyD88, Toll-like receptor 3, or the recently described DexD/H-box helicase DDX1 sensor had no or a weak effect on IFN-␤ induction, suggesting that the RIG-I-like receptor pathway is specifically engaged for BTV sensing. Moreover, we also showed that overexpression of either RIG-I or MDA5 impaired BTV expression in infected A549 cells. Overall, this indicates that RIG-I and MDA5 can both contribute to the recognition and control of BTV infection.

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Section: Discussionmentioning

confidence: 69%

Sensing and Control of Bluetongue Virus Infection in Epithelial Cells via RIG-I and MDA5 Helicases

Chauveau

Doceul

Lara

et al. 2012

J Virol

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“…The LR gene contains two major open reading frames (ORFs), ORF2 and ORF1, and two reading frames that lack an initiating methionine (RF-C and RF-B) (16). Two microRNAs encoded within the LR gene inhibit BHV-1 infected cell protein 0 (bICP0) expression (17) and promote cell survival (18). A mutant BHV-1 strain with three stop codons at the N terminus of ORF2 (LR mutant virus) does not express detectable levels of ORF2 or RF-C (19) but expresses reduced levels of ORF1 during the productive infection of cultured cells (20).…”

mentioning

confidence: 99%

A Bovine Herpesvirus 1 Protein Expressed in Latently Infected Neurons (ORF2) Promotes Neurite Sprouting in the Presence of Activated Notch1 or Notch3

Sinani

Silva

Jones

2013

J Virol

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(ORF2) is not reactivated from latency, in part because it induces higher levels of apoptosis in infected neurons. ORF2 inhibits apoptosis in transiently transfected cells, suggesting that it plays a crucial role in the latency-reactivation cycle. ORF2 also interacts with Notch1 or Notch3 and inhibits its ability to trans activate certain viral promoters. Notch3 RNA and protein levels are increased during reactivation from latency, suggesting that Notch may promote reactivation. Activated Notch signaling interferes with neuronal differentiation, in part because neurite and axon generation is blocked. In this study, we demonstrated that ORF2 promotes neurite formation in mouse neuroblastoma cells overexpressing Notch1 or Notch3. ORF2 also interfered with Notch-mediated trans activation of the promoter that regulates the expression of Hairy Enhancer of Split 5, an inhibitor of neurite formation. Additional studies provided evidence that ORF2 promotes the degradation of Notch3, but not that of Notch1, in a proteasome-dependent manner. In summary, these studies suggest that ORF2 promotes a mature neuronal phenotype that enhances the survival of infected neurons and consequently increases the pool of latently infected neurons.

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“…It will also be essential to confirm any findings in vivo in regard to BoHV-1, miRNA expression and virulence. The importance of in vivo validation is demonstrated by studies focused on the BoHV-1 latency which have identified viral miRNAs not detected in cultured bovine cells infected with replicating virus [55,56]. The development of BoHV-1 GMV that have modified miRNA patterns that influence properties such as virulence, establishment of latency and reactivation from latency are yet to be explored.…”

Section: Vaccination Against Brdmentioning

confidence: 99%

Understanding the molecular basis of disease is crucial to improving the design and construction of herpesviral vectors for veterinary vaccines

Mahony

2015

Vaccine

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Two MicroRNAs Encoded within the Bovine Herpesvirus 1 Latency-Related Gene Promote Cell Survival by Interacting with RIG-I and Stimulating NF-κB-Dependent Transcription and Beta Interferon Signaling Pathways

Cited by 17 publications

References 91 publications

Sensing and Control of Bluetongue Virus Infection in Epithelial Cells via RIG-I and MDA5 Helicases

Sensing and Control of Bluetongue Virus Infection in Epithelial Cells via RIG-I and MDA5 Helicases

A Bovine Herpesvirus 1 Protein Expressed in Latently Infected Neurons (ORF2) Promotes Neurite Sprouting in the Presence of Activated Notch1 or Notch3

Understanding the molecular basis of disease is crucial to improving the design and construction of herpesviral vectors for veterinary vaccines

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