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

By R. Randall, S. Goodbourn. 2008

1,684 citations recorded by the source corpus.

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.

Subfields: Epidemiology, Genetics, Immunology

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Epidemiology

1. James J. Collins
2. R. Randall

In Genetics

1. Alexander Meissner
2. James J. Collins
3. Zachary D. Smith
4. Derrick J. Rossi
5. Dongbin Xiu

In Immunology

1. James J. Collins
2. R. Randall
3. Derrick J. Rossi
4. N. Regamey
5. M. Edwards
6. M. Vareille
7. E. Kieninger

Citations in the corpus

• Highly efficient reprogramming to pluripotency and directed differentiation of human cells using synthetic modified mRNA (2010, background): “It is known that cellular antiviral defenses can self-prime through a positive-feedback loop involving autocrine and paracrine signaling by type I interferons (Randall and Goodbourn, 2008).”
• The multifunctional NS1 protein of influenza A viruses. (2008, background): “Type I IFNs, such as IFN-a or IFN-b, are soluble cytokines that are synthesized and secreted by cells in response to virus infection, and act in both an autocrine and paracrine manner to upregulate the expression of .300 IFN-stimulated antiviral genes (Randall & Goodbourn, 2008).”
• The Airway Epithelium: Soldier in the Fight against Respiratory Viruses (2011, background): “By interfering with IFN production, respiratory viruses can block multiple antiviral pathways simultaneously, including IFN synthesis, ISG induction, and recruitment of inflammatory cells (71, 226).”
• Interferon-stimulated genes and their antiviral effector functions (2011, neutral): “The experimental observation of these intermediate phenotypes supports the hypothesis that IFN effectors work in combination to achieve a fully functional antiviral state [23].”