Effect of ORF119 gene deletion on the replication and virulence of orf virus

Qiao, Jun; Yang, Huiqin; Peng, Yanhui; Meng, Qiong; C, Chen; Ma, Yanhui; Xie, Kui; Liu, T L; Cai, Xixu; Chen, C F

doi:10.4149/av_2015_03_257

Cited by 4 publications

(6 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mitochondrial protein coded by this gene was recently described as being capable of increasing cell apoptosis ( 44 , 45 ). Despite this finding, our observations and a previous report showed no phenotypic modification in the virus cycle regarding this gene deletion ( 46 ).…”

Section: Discussioncontrasting

confidence: 99%

See 1 more Smart Citation

Human Infection with Orf Virus and Description of Its Whole Genome, France, 2017

Andréani¹,

Fongue²,

Khalil³

et al. 2019

Emerg. Infect. Dis.

View full text Add to dashboard Cite

Zoonotic transmission of parapoxvirus from animals to humans has been reported; clinical manifestations are skin lesions on the fingers and hands after contact with infected animals. We report a human infection clinically suspected as being ecthyma contagiosum. The patient, a 65-year-old woman, had 3 nodules on her hands. She reported contact with a sheep during the Aïd-el-Fitr festival in France during 2017. We isolated the parapoxvirus orf virus from these nodules by using a nonconventional cell and sequenced the orf genome. We identified a novel orf virus genome and compared it with genomes of other orf viruses. More research is needed on the genus Parapoxvirus to understand worldwide distribution of and infection by orf virus, especially transmission between goats and sheep.

show abstract

Section: Discussioncontrasting

confidence: 99%

“…This deletion has been implied in cell apoptosis ( 44 , 45 ). Nevertheless, deletion of this gene did not affect the virus cycle and strain virulence ( 46 ).…”

Section: Resultsmentioning

confidence: 99%

Human Infection with Orf Virus and Description of Its Whole Genome, France, 2017

Andréani¹,

Fongue²,

Khalil³

et al. 2019

Emerg. Infect. Dis.

View full text Add to dashboard Cite

show abstract

“…The attenuated phenotype of infection likely indicates improved host control of ORFV infection in the absence of ORFV119 ( S8 Fig ). Our results are at variance with a previous report where no differences in virulence and pathogenesis were observed between wild type and ORFV119 deletion viruses [ 71 ]. The discrepancy likely reflects differences in viral strains (IA82 vs SHZ1), extent of genomic deletion, and/or in vitro conditions for virus propagation.…”

Section: Discussioncontrasting

confidence: 99%

A parapoxviral virion protein targets the retinoblastoma protein to inhibit NF-κB signaling

et al. 2017

View full text Add to dashboard Cite

Poxviruses have evolved multiple strategies to subvert signaling by Nuclear Factor κB (NF-κB), a crucial regulator of host innate immune responses. Here, we describe an orf virus (ORFV) virion-associated protein, ORFV119, which inhibits NF-κB signaling very early in infection (≤ 30 min post infection). ORFV119 NF-κB inhibitory activity was found unimpaired upon translation inhibition, suggesting that virion ORFV119 alone is responsible for early interference in signaling. A C-terminal LxCxE motif in ORFV119 enabled the protein to interact with the retinoblastoma protein (pRb) a multifunctional protein best known for its tumor suppressor activity. Notably, experiments using a recombinant virus containing an ORFV119 mutation which abrogates its interaction with pRb together with experiments performed in cells lacking or with reduced pRb levels indicate that ORFV119 mediated inhibition of NF-κB signaling is largely pRb dependent. ORFV119 was shown to inhibit IKK complex activation early in infection. Consistent with IKK inhibition, ORFV119 also interacted with TNF receptor associated factor 2 (TRAF2), an adaptor protein recruited to signaling complexes upstream of IKK in infected cells. ORFV119-TRAF2 interaction was enhanced in the presence of pRb, suggesting that ORFV119-pRb complex is required for efficient interaction with TRAF2. Additionally, transient expression of ORFV119 in uninfected cells was sufficient to inhibit TNFα-induced IKK activation and NF-κB signaling, indicating that no other viral proteins are required for the effect. Infection of sheep with ORFV lacking the ORFV119 gene led to attenuated disease phenotype, indicating that ORFV119 contributes to virulence in the natural host. ORFV119 represents the first poxviral protein to interfere with NF-κB signaling through interaction with pRb.

show abstract

“…Interestingly, among the region of ORFs 118–120, the non-coding fragments are almost as long as the coding fragments ( Li et al, 2015 ). According to this insight, we speculate that these areas might be part of the coding regions in early stages of orf virus evolution ( Qiao et al, 2015 ). It is noteworthy, that ORFV119 was recently revealed able to inhibit NF-kappa B signaling through interaction with pRb ( Nagendraprabhu et al, 2017 ).…”

Section: Introductionmentioning

confidence: 83%

“…However, further research is necessary to fully characterize this process, such as identifying the functional domain of ORFV119. Because some studies have reported that the deletion of the ORF119 gene had no significant effect on viral replication and virulence ( Qiao et al, 2015 ), future studies should include more ORFV strains, since virulence and genomes vary greatly among ORFV strains, viral recombination and subsequent in vivo experiments ( Delhon et al, 2004 ; Chi et al, 2015 ; Li et al, 2015 ). In addition, the relevance and interaction between regulation of NF-κB and regulation of apoptosis need to be explored further ( Nagendraprabhu et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Orf Virus Encoded Protein ORFV119 Induces Cell Apoptosis Through the Extrinsic and Intrinsic Pathways

Chen

Deng

et al. 2018

Front. Microbiol.

View full text Add to dashboard Cite

Apoptosis, a significant form of cell death, has a leading role in the host cell defense against virus infection. Viruses have evolved a series of strategies that block apoptosis during the early stage of viral infection to enhance viral replication, and induce apoptosis in the late stages to facilitate viral particle release from the cells. Here we show that orf virus (ORFV), the causative agent of orf, encodes an apoptosis-inducing protein ORFV119. ORFV119 targets the mitochondria in host cells, inhibits cell proliferation, and induces cell apoptosis. Protein array data indicated that ORFV119 could induce apoptosis via up-regulation of Smac, Bak, and Bax and down-regulation of anti-apoptotic proteins Bcl-2 and cIAP-2. Activation of caspase-9 and caspase-3, and consequent PARP cleavage, ultimately lead to apoptosis. ORFV119 could also directly activate caspase-8 and induce Bid, involved in the extrinsic pathway, to achieve cell death. Furthermore, sequence analysis and experiments with mutants of ORFV119 introduced revealed that ORFV119 contains a key N-terminal domain that is necessary and sufficient to direct the protein to the mitochondria. Together, we report, for the first time, the identification of the novel apoptosis-inducing protein ORFV119 encoded by a parapoxvirus. This provides an important reference for the study of pathogenesis, identification of immunomodulation mechanisms of ORFV, and may lead to new strategies for orf disease control.

show abstract

Effect of ORF119 gene deletion on the replication and virulence of orf virus

Cited by 4 publications

References 30 publications

Human Infection with Orf Virus and Description of Its Whole Genome, France, 2017

Human Infection with Orf Virus and Description of Its Whole Genome, France, 2017

A parapoxviral virion protein targets the retinoblastoma protein to inhibit NF-κB signaling

Orf Virus Encoded Protein ORFV119 Induces Cell Apoptosis Through the Extrinsic and Intrinsic Pathways

Contact Info

Product

Resources

About