A Vaccinia Virus Deletion Mutant Reveals the Presence of Additional Inhibitors of NF-κB

Fagan-Garcia, Katharine; Barry, Michèle

doi:10.1128/jvi.01267-10

Cited by 13 publications

(18 citation statements)

References 69 publications

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“…The generation of nuclear extracts (NE) and cytoplasmic extracts (CE) were performed as previously described (43). HeLa cells (10 6 ) were either mock infected or infected with ECTVgal or ECTV⌬150 at an MOI of 5 for 16 h. Alternatively, cells were transfected with negative-control siRNA (Qiagen), cullin-1 siRNA, or cullin-3 siRNA for 72 h to knock down cullin-1 or cullin-3.…”

Section: Methodsmentioning

confidence: 99%

Ectromelia Virus Encodes a BTB/kelch Protein, EVM150, That Inhibits NF-κB Signaling

Wang

Burles

Couturier

et al. 2014

J Virol

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The NF-B signaling pathway plays a critical role in inflammation and innate immunity. Consequently, many viruses have evolved strategies to inhibit NF-B in order to facilitate replication and evasion of the host immune response. Recently, we determined that ectromelia virus, the causative agent of mousepox, contains a family of four BTB/kelch proteins that interact with cullin-3-based ubiquitin ligases. We demonstrate here that expression of EVM150, one of the four BTB/kelch proteins, inhibited NF-B activation induced by tumor necrosis factor alpha (TNF-␣) and interleukin-1␤ (

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Section: Methodsmentioning

confidence: 99%

Ectromelia Virus Encodes a BTB/kelch Protein, EVM150, That Inhibits NF-κB Signaling

Wang

Burles

Couturier

et al. 2014

J Virol

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“…The original report suggested that these viruses are capable of forming plaques on the human cell line MRC-5 (Perkus et al, 1991). Later reports showed that vP811 can form infectious virions on HeLa (Fagan-Garcia & Barry, 2011) and establish a persistent infection of Jurkat cells (Melana & Pogo, 2005). Furthermore, in single-step growth curves, vP811 replicates as well as Copenhagen in BGMK and A549 cells, but forms smaller plaques than Copenhagen on BS-C-1, A549 and BGMK cells (Burles et al, 2014;Sumner et al, 2014).…”

Section: Essential Genes As Defined By Conservation and Large Deletionsmentioning

confidence: 99%

Redundancy complicates the definition of essential genes for vaccinia virus

Dobson

Tscharke

2015

Journal of General Virology

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Vaccinia virus (VACV) genes are characterized as either essential or non-essential for growth in culture. It seems intuitively obvious that if a gene can be deleted without imparting a growth defect in vitro it does not have a function related to basic replication or spread. However, this interpretation relies on the untested assumption that there is no redundancy across the genes that have roles in growth in cell culture. First, we provide a comprehensive summary of the literature that describes the essential genes of VACV. Next, we looked for interactions between large blocks of non-essential genes located at the ends of the genome by investigating sets of VACVs with large deletions at the genomic termini. Viruses with deletions at either end of the genome behaved as expected, exhibiting only mild or host-range defects. In contrast, combining deletions at both ends of the genome for the VACV Western Reserve (WR) strain caused a devastating growth defect on all cell lines tested. Unexpectedly, we found that the well-studied VACV growth factor homologue encoded by C11R has a role in growth in vitro that is exposed when 42 genes are absent from the left end of the VACV WR genome. These results demonstrate that some non-essential genes contribute to basic viral growth, but redundancy means these functions are not revealed by single-gene-deletion mutants.

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“…Lastly, protein C4 inhibits NF-κB at or downstream of the IKK complex [35]. However, genetic evidence predicts additional VACV inhibitor(s) of NF-κB activation that stabilise phosphorylated IκBα (p-IκBα) [36].…”

Section: Introductionmentioning

confidence: 99%

Poxvirus Targeting of E3 Ligase β-TrCP by Molecular Mimicry: A Mechanism to Inhibit NF-κB Activation and Promote Immune Evasion and Virulence

et al. 2013

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The transcription factor NF-κB is essential for immune responses against pathogens and its activation requires the phosphorylation, ubiquitination and proteasomal degradation of IκBα. Here we describe an inhibitor of NF-κB from vaccinia virus that has a closely related counterpart in variola virus, the cause of smallpox, and mechanistic similarity with the HIV protein Vpu. Protein A49 blocks NF-κB activation by molecular mimicry and contains a motif conserved in IκBα which, in IκBα, is phosphorylated by IKKβ causing ubiquitination and degradation. Like IκBα, A49 binds the E3 ligase β-TrCP, thereby preventing ubiquitination and degradation of IκBα. Consequently, A49 stabilised phosphorylated IκBα (p-IκBα) and its interaction with p65, so preventing p65 nuclear translocation. Serine-to-alanine mutagenesis within the IκBα-like motif of A49 abolished β-TrCP binding, stabilisation of p-IκBα and inhibition of NF-κB activation. Remarkably, despite encoding nine other inhibitors of NF-κB, a VACV lacking A49 showed reduced virulence in vivo.

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A Vaccinia Virus Deletion Mutant Reveals the Presence of Additional Inhibitors of NF-κB

Cited by 13 publications

References 69 publications

Ectromelia Virus Encodes a BTB/kelch Protein, EVM150, That Inhibits NF-κB Signaling

Ectromelia Virus Encodes a BTB/kelch Protein, EVM150, That Inhibits NF-κB Signaling

Redundancy complicates the definition of essential genes for vaccinia virus

Poxvirus Targeting of E3 Ligase β-TrCP by Molecular Mimicry: A Mechanism to Inhibit NF-κB Activation and Promote Immune Evasion and Virulence

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