Virus Replication in Engineered Human Cells That Do Not Respond to Interferons

Young, D. F.; Andrejeva, L.; Livingstone, A.; Goodbourn, Stephen; Lamb, Robert A.; Collins, Peter L.; Elliott, Richard M.; Randall, R. E.

doi:10.1128/jvi.77.3.2174-2181.2003

Cited by 76 publications

(91 citation statements)

References 23 publications

(20 reference statements)

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“…Consistent with this, many wild-type viruses form bigger plaques on cells engineered to be non-responsive to IFN than on the parental cells (Young et al, 2003). Consequently, until viruses can synthesize enough of the viral IFN antagonist(s) to limit the IFN response, it is also important for viruses to keep production of any potential inducer(s) of IFN to a minimum.…”

Section: General Considerations Of How Viruses Evade the Ifn Responsementioning

confidence: 76%

“…For example, the NSs protein of Bunyamwera virus (BUNV) inhibits cellular mRNA transcription by blocking the activity of RNA polymerase II (Thomas et al, 2004). However, a recombinant BUNV that does not encode a NSs protein is pathogenic in IFN-a/b receptor-knockout mice and grows to high titres in cells that do not produce IFN (Weber et al, 2002;Young et al, 2003). Similarly, the NSs protein of La Crosse virus (LACV) serves primarily to suppress the IFN response of mammalian hosts (Blakqori et al, 2007).…”

Section: General Considerations Of How Viruses Evade the Ifn Responsementioning

confidence: 99%

“…Presumably, PIV5 (and closely related paramyxoviruses) are less concerned with the RIG-I-induction pathway, as they limit the production of the inducer of RIG-I (Dillon & Parks, 2007). Nevertheless, it is of note that the ability of paramyxoviruses to circumvent the IFN response may not be absolute (Young et al, 2003).…”

Section: Consequences For the Virus And Hostmentioning

confidence: 99%

“…This implies that, in a normal acute infection, the IFN response probably constitutes a constant selective pressure that keeps viruses maximally fit in terms of replication speed and competence, and in the maintenance of mechanisms to circumvent the IFN response. It also suggests that the efficiency by which a given virus overcomes the IFN response may be extremely important in terms of its pathogenesis and host range (Young et al, 2003). Viral IFN antagonists are often multifunctional proteins and their different properties may vary in importance at different stages of the virus replication cycle.…”

Section: General Considerations Of How Viruses Evade the Ifn Responsementioning

confidence: 99%

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Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures

Randall

Goodbourn

2008

Journal of General Virology

1,389

1,420

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The interferon (IFN) system is an extremely powerful antiviral response that is capable of controlling most, if not all, virus infections in the absence of adaptive immunity. However, viruses can still replicate and cause disease in vivo, because they have some strategy for at least partially circumventing the IFN response. We reviewed this topic in 2000 [Goodbourn, S., Didcock, L. & Randall, R. E. (2000). J Gen Virol 81, 2341-2364] but, since then, a great deal has been discovered about the molecular mechanisms of the IFN response and how different viruses circumvent it. This information is of fundamental interest, but may also have practical application in the design and manufacture of attenuated virus vaccines and the development of novel antiviral drugs. In the first part of this review, we describe how viruses activate the IFN system, how IFNs induce transcription of their target genes and the mechanism of action of IFN-induced proteins with antiviral action. In the second part, we describe how viruses circumvent the IFN response. Here, we reflect upon possible consequences for both the virus and host of the different strategies that viruses have evolved and discuss whether certain viruses have exploited the IFN response to modulate their life cycle (e.g. to establish and maintain persistent/latent infections), whether perturbation of the IFN response by persistent infections can lead to chronic disease, and the importance of the IFN system as a species barrier to virus infections. Lastly, we briefly describe applied aspects that arise from an increase in our knowledge in this area, including vaccine design and manufacture, the development of novel antiviral drugs and the use of IFN-sensitive oncolytic viruses in the treatment of cancer. Biology of the interferon systemThe interferons (IFNs) are a group of secreted cytokines that elicit distinct antiviral effects. They are grouped into three classes called type I, II and III IFNs, according to their amino acid sequence. Type I IFNs (discovered in 1957;Isaacs & Lindenmann, 1957) comprise a large group of molecules; mammals have multiple distinct IFN-a genes (13 in man), one to three IFN-b genes (one in man) and other genes, such as IFN-v, -e, -t, -d and -k. The IFN-a and -b genes are induced directly in response to viral infection, whereas IFN-v, -e, -d and -k play less well-defined roles, such as regulators of maternal recognition in pregnancy. Thus, rather than use the term 'type I IFN', we will use IFN-a/b when referring to the virally induced cytokines. Although the multigenic nature of IFN-a has been known for over 20 years, the significance of this is still debatedi.e. whether these genes are expressed differentially in distinct cell types, whether they are inducible by different types of viruses or whether they are functionally specialized (Brideau-Andersen et al., 2007). For the rest of this review, we will not distinguish between IFN-a subtypes. Type III IFNs have been described more recently and comprise IFNl1, -l2 and -l3, also referred to as IL-2...

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Section: General Considerations Of How Viruses Evade the Ifn Responsementioning

confidence: 76%

Section: General Considerations Of How Viruses Evade the Ifn Responsementioning

confidence: 99%

Section: Consequences For the Virus And Hostmentioning

confidence: 99%

Section: General Considerations Of How Viruses Evade the Ifn Responsementioning

confidence: 99%

See 2 more Smart Citations

Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures

Randall

Goodbourn

2008

Journal of General Virology

1,389

1,420

View full text Add to dashboard Cite

show abstract

“…It is suggested that the efficiency with which a given virus overcomes the IFN response may be extremely important for its pathogenesis and host range (34,35). Strategies used by virus-encoded IFN antagonists include general inhibition of cellular gene expression, sequestration of molecules in the IFN-induction pathway, and cleavage or degradation of innate immune components (reviewed in Refs.…”

mentioning

confidence: 99%

Human Bocavirus NP1 Inhibits IFN-β Production by Blocking Association of IFN Regulatory Factor 3 with IFNB Promoter

Zhang

Zheng

Luo

et al. 2012

The Journal of Immunology

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Human bocavirus (HBoV) mainly infects young children. Although many infected children suffer from respiratory or gastroenteric tract diseases, an association between HBoV and these diseases is not definite. Because modulation of type I IFN is crucial for viruses to establish efficient replication, in this study, we tested whether HBoV modulates type I IFN production. We observed that a nearly full-length HBoV clone significantly reduced both Sendai virus (SeV)- and poly(deoxyadenylic-thymidylic) acid-induced IFN-β production. Further study showed that NP1 blocked IFN-β activation in response to SeV, poly(deoxyadenylic-thymidylic) acid, and IFN-β pathway inducers, including retinoic acid-inducible protein I, mitochondrial antiviral signaling protein, inhibitor of κB kinase ε, and TANK-binding kinase 1. In addition, NP1 interfered with IRF-3–responsive PRD(III-I) promoter activated by SeV and a constitutively active mutant of IRF-3 (IRF-3/5D). Although NP1 suppressed the IRF-3 pathway, it did not affect IRF-3 activation processes, including phosphorylation, dimerization, and nuclear translocation. Coimmunoprecipitation assays confirmed the interaction between NP1 and IRF-3. Additional deletion mutagenesis and coimmunoprecipitation assays revealed that NP1 bound to the DNA-binding domain of IRF-3, resulting in the interruption of an association between IRF-3 and IFNB promoter. Altogether, our results indicate that HBoV NP1 blocks IFN production through a unique mechanism. To our knowledge, this is the first study to investigate the modulation of innate immunity by HBoV. Our findings suggest a potential immune-evasion mechanism used by HBoV and provide a basis for better understanding HBoV pathogenesis.

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Introduction

Bridgen¹

2012

Reverse Genetics of RNA Viruses

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Virus Replication in Engineered Human Cells That Do Not Respond to Interferons

Cited by 76 publications

References 23 publications

Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures

Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures

Human Bocavirus NP1 Inhibits IFN-β Production by Blocking Association of IFN Regulatory Factor 3 with IFNB Promoter

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