from Helene MinYi Liu and Michael Gale Jr writing in Viruses and Interferon: Current Research:

Mammalian cells respond to virus challenge by initiating an intracellular innate immune response that is designed to limit virus replication and to inform and modulate the ensuing adaptive immune response. Innate immune defenses are characterized by pathogen recognition receptor signaling that mediates the expression of antiviral gene products, the production of interferon α/β (IFN) and interferon-stimulated genes, and the secretion of other proinflammatory cytokines from the site of infection. Hepatitis C virus (HCV) confers a chronic infection of the liver in nearly 200 million people around the world. Hepatic innate immune defenses impose the front line of protection against HCV replication and pathogenesis. HCV infection is treated with IFN-based therapy. However, HCV most often evades hepatic innate immunity and responds overall poorly to therapy to thereby persist and a run a chronic disease course. HCV persistence has been linked to a complex combination of virus-host interactions that disrupt intracellular innate immune signaling pathways and attenuate the antiviral actions of IFN. Viral regulation of these processes breaks a critical cross-talk between innate and adaptive immunity to attenuate antiviral immune defenses and provide a foundation for chronic HCV infection.

Further reading: Viruses and Interferon: Current Research

from Duane J Gubler writing in Molecular Virology and Control of Flaviviruses:

The flaviviruses (genus Flavivirus) are among the most important pathogens infecting humans and domestic animals, causing hundreds of millions of infections annually. They have a global distribution and cause a broad spectrum of illness ranging from mild viral syndrome to severe and fatal hemorrhagic and neurologic disease. The genus is made up of a diverse group of 53 viral species that have evolved into three distinct groups with very different transmission cycles. The vector-borne group is transmitted among vertebrate hosts by hematophagous arthropods (mosquitoes and ticks), the no-known vector group is transmitted directly among vertebrate animals and the arthropod group is transmitted directly among arthropods. This chapter reviews the history, the present status and future trends of flaviviruses, using some of the more important species as case studies.

Further reading: Molecular Virology and Control of Flaviviruses

from Ken E. Olson and Carol D. Blair writing in Molecular Virology and Control of Flaviviruses:

Flaviviruses such as dengue, yellow fever and West Nile viruses continue to cause a significant amount of disease in humans. Most flaviviruses are maintained in nature by cycling between hematophagus arthropod vectors and vertebrate hosts, and the viruses need to replicate in both vectors and hosts. This review focuses on flavivirus-vector interactions to present a current understanding of events and processes that lead to vector infection, virus amplification and dissemination, transmission. This chapter will focus mainly on DENVs and their interactions with Aedes aegypti, but will include interactions between other flaviviruses and their vectors where approriate. Flavivirus-mosquito cell interactions will be discussed first to give the reader a cellular view of the infection process but this will be followed with a view of the infection process in vectors. This review will describe flavivirus interactions with the vector's innate immune (Toll, Jak-Stat, apoptosis) and antiviral (RNA interference) pathways and discuss flavivirus evolution and its consequences for vector infection, DENV transmission and genotype displacement. The review will dicuss how our understanding of vector genetics is enhanced by the availability of genome databases for A. aegypti and Culex quinquefasciatus, tissue-specific transcriptomes and microarrays and small RNA databases. The chapter will also discuss RNA silencing and vector transgenesis as tools for defining gene function. Finally, we will review several recently described vector-based approaches that may result in new strategies for flavivrus disease control.

Further reading: Molecular Virology and Control of Flaviviruses

"Overall, this book provides a timely and useful review of topics relevant to the interface of small RNA biology and virology. Chapters were written to stand alone and are therefore best read individually ... a good addition to institutional libraries." from Eva Gottwein (Chicago, USA) writing in The Quarterly Review of Biology (2012) 87: 66-67. read more ...

RNA Interference and Viruses: Current Innovations and Future Trends Edited by: Miguel Angel Martínez ISBN: 978-1-904455-56-1 Publisher: Caister Academic Press Publication Date: February 2010 Cover: hardback "a timely and useful review" (Quart. Rev. Biol.)

from Richard J. Kuhn writing in Molecular Virology and Control of Flaviviruses:

Flavivirus virions form in the endoplasmic reticulum (ER) with the recruitment of genome RNA, capsid protein, and the envelope (E) and precursor to the membrane proteins (prM). The nascent particles acquire a lipid bilayer as they bud into the ER lumen in an immature form. Glycosylation and subsequent processing of the particles occur as they proceed through the cellular secretory system. In the low pH that is encountered in the trans-Golgi network, cellular furin activates the particles by cleavage of prM into M. The particles are released from the cell in a mature and infectious form. The observations demonstrate the significant conformational and translational movements of the viral structural proteins during the virus life cycle and suggest the particles have substantial dynamic capabilities. These properties have been substantiated by analyses of antibody binding to virions and suggest novel targets for future therapeutic intervention strategies.

Further reading: Molecular Virology and Control of Flaviviruses

from Scott B. Halstead writing in Molecular Virology and Control of Flaviviruses:

Eight flaviviruses cause significant morbidity and mortality around the globe: yellow fever (YF), Japanese encephalitis (JE), Tick-borne encephalitis (TBE), dengue 1, 2, 3, 4 and West Nile (WN). Four, YF, JE, TBE and WN are zoonoses, with the consequence that vaccines are the only means of protecting humans. The successful YF 17D vaccine, introduced in 1937, produced dramatic reductions in epidemic activity. Effective killed JE and TBE vaccines were introduced in the middle of the 20th century. Unacceptable adverse events have prompted change from a mouse-brain killed JE vaccine to safer and more effective second generation JE vaccines. These may come into wide use to effectively prevent this severe disease in the huge populations of Asia - North, South and Southeast. The dengue viruses produce many millions of infections annually due to transmission by a successful global mosquito vector. As mosquito control has failed, several dengue vaccines are in varying stages of development. A tetravalent chimeric vaccine that splices structural genes of the four dengue viruses onto a 17D YF backbone is in Phase III clinical testing. For each of the eight flaviviruses, clinical disease, epidemiology, vaccine development history, vaccine useage, precautions and adverse events are briefly presented.

Further reading: Molecular Virology and Control of Flaviviruses

from Justin A. Roby, Anneke Funk, and Alexander A. Khromykh writing in Molecular Virology and Control of Flaviviruses:

The replication and assembly of Flaviviruses are complex procedures, which require the efficient coordination of a number of different steps. These stages are highly organized temporally and spatially in the infected cell and require the virus-induced establishment of host-derived membrane structures. Flavivirus RNA structures, non-structural proteins and host factors actively participate in the replication of genomic RNA within vesicle packets (VP). Progeny (+) strand RNA exits the VP pore and is incorporated into nucleocapsids by the capsid protein. Nucleocapsids are then presumably transported into the lumen of the endoplasmic reticulum at sites directly opposed to the VP pore during formation of the prM-E studded lipid envelope. These immature virions are trafficked to the Golgi network in individual vesicles for glycoprotein maturation and furin-directed prM cleavage. Mature virions (with associated, cleaved prM) are then secreted into the extracellular milieu.

Further reading: Molecular Virology and Control of Flaviviruses

from Gregory D. Ebel and Laura D. Kramer writing in Molecular Virology and Control of Flaviviruses:

Flavivirus fitness is inextricably linked to the ability of a particular agent to be efficiently transmitted among relevant hosts in natural transmission cycles. Thus, fitness is an inherent component of the virus-host relationship. The mechanisms through which virus fitness is maximized are poorly understood, but have recently been examined in increasing detail. This chapter examines recent developments in the study of flavivirus fitness from both observational and experimental studies, highlighting important emergent and/or resurgent tick- and mosquito-borne members of the flavivirus genus.

Further reading: Molecular Virology and Control of Flaviviruses

from Elizabeth Hunsperger writing in Molecular Virology and Control of Flaviviruses:

Within the family of Flaviviridae there are many medically important viruses that cause human disease worldwide. These viruses were originally categorized based on phenotype due to their antigenic relatedness and placed within groups, subgroups and types and later confirmed with nucleic acid sequence analysis. Diagnosis of disease caused by flaviviruses has been primarily based on serological identification of anti-viral antibodies and virus isolation. Some of the classic serological techniques of hemagglutination inhibition assay and complement fixation were replaced with the enzyme linked immunosorbent assay (ELISA) for the detection of IgM, IgG and IgA antibodies primarily due to ease-of-use. The plaque reduction neutralization test (PRNT) provided the specificity needed for virus identification following a positive serological test by ELISA. The development of polymerase chain reaction (PCR) assays improved the ability to detect virus nucleic acid sequence when viral isolates were not obtained. Because reverse transcriptase PCR (RT-PCR) assays are easy to perform, have increased sensitivity and provide virus identification in a short period of time, RT-PCR has essentially replaced isolation techniques for rapid diagnosis. However, virus isolation is still essential for genetic analysis. The future of flaviviral disease diagnosis is new platforms for antibody and nucleic acid detection as well as the development of point-of-care diagnostics for clinical management

Further reading: Molecular Virology and Control of Flaviviruses

from Qing-Yin Wang, Yen-Liang Chen, Siew Pheng Lim, and Pei-Yong Shi writing in Molecular Virology and Control of Flaviviruses:

Many flaviviruses are human pathogens of global importance, but no clinically approved antiviral therapy is currently available to manage these diseases. Both pharmaceutical industry and academia have invested considerable efforts over the past decade on finding the flavivirus antivirals using modern drug discovery. Various high-throughput compatible target-based and cell-based assays have been developed and implemented. In this chapter, we describe in details the methodologies developed for screening inhibitors against dengue virus, and the lessons learned from our screening campaigns. Based on our experience on dengue virus and the status of hepatitis C virus drug discovery, we propose that a combined target-based approach (e.g., viral polymerase, protease, and envelope) and a cell-based approach (e.g., virus infection and replicon assays) should be persistently pursued to develop flavivirus antiviral therapy.

Further reading: Molecular Virology and Control of Flaviviruses

from Christopher F. Basler and Gaya K. Amarasinghe writing in Viruses and Interferon: Current Research:

Viral hemorrhagic fever, a clinical syndrome characterized by fever, shock and bleeding, can be caused in humans by members of several RNA virus families, including filoviruses, bunyaviruses, arenaviruses and flaviviruses. None of the hemorrhagic fever viruses uniformly cause hemorrhage in humans. However, some viruses show greater propensity to cause severe, life threatening disease than do others. Because of their potential to cause life threatening disease, these viruses are public health concerns and many of the hemorrhagic fever viruses are considered to be potential weapons of terror. Recent emphasis on these viruses has prompted research into the mechanisms by which they interact with and evade host innate immune responses, particularly antiviral interferon (IFN) responses. Research has identified a variety of mechanisms of innate immune antagonism, and data from filovirus and bunyavirus systems links these functions to virulence. This sets the stage for studies to evaluate how specific mechanisms of IFN evasion contribute to the clinical manifestations of viral hemorrhagic fever.

Further reading: Viruses and Interferon: Current Research

from William P. Halford and Bryan M. Gebhardt writing in Viruses and Interferon: Current Research:

Herpes simplex virus (HSV) establishes latent infections as a consequence of a non-cytolytic immune response that represses HSV replication, but fails to destroy neurons that harbor HSV's genetic material. It has become increasingly evident that, in both mice and men, the host interferon system plays a critical role in tipping HSV's latency-replication balance in favor of latency. HSV can resist interferon-induced repression provided that HSV's two interferon antagonists, ICP0 and ICP34.5, are synthesized. Failure to synthesize either protein renders HSV interferon-sensitive and prone to establishing latent infections. Intriguingly, ICP0 and ICP34.5 are encoded within HSV's latency-regulating RL regions. We propose that differential synthesis of ICP0 and ICP34.5 may endow HSV with the capacity to 'choose' between latency and replication in vivo. HSV may choose to establish a latent infection by downregulating ICP0 or ICP34.5, and render itself sensitive to the interferon-induced antiviral state. Conversely, synthesis of ICP0 and ICP34.5 may ensure that HSV resists interferon-induced repression and completes another cycle of replication.

Further reading: Viruses and Interferon: Current Research

from Mark Schreiber, Joel Leong, and Martin Hibberd writing in Molecular Virology and Control of Flaviviruses:

Dengue fever is an acute viral infection that can produce a wide spectrum of disease outcomes in patients, ranging from mild or even asymptomatic fever to severe manifestations including hemorrhagic fever and shock. With the incidence of the severe forms increasing in most tropical countries as well as an overall increase in dengue incidence, dengue fever is becoming a significant burden on the health systems of affected countries. In this review, we examine the clinical definitions and presentation of mild and severe dengue as well as recent research into the underlying molecular mechanisms of the differential host response. Finally, we will examine how host responses from the early phase of the disease might be useful as biomarkers for predicting the eventual disease outcome.

Further reading: Molecular Virology and Control of Flaviviruses

from Gijs A. Versteeg and Adolfo García-Sastre writing in Viruses and Interferon: Current Research:

Influenza viruses are the etiological agents of seasonal influenza outbreaks as well as three devastating influenza pandemics in the 20th century and the 2009 swine-origin H1N1 pandemic. Like most viruses that cause significant disease, influenza viruses have developed means to circumvent the induction and effects of the innate immune system. Unlike most other RNA viruses, influenza viruses replicate in the nucleus, rather than in the cytoplasm. This distinguishing feature makes the interactions of influenza viruses with their hosts both complex and unique, and requires a well-orchestrated manipulation of many cellular processes. This includes the interferon (IFN) response, a key innate immune pathway, critical for limiting virus replication. To cope with the IFN burden, influenza viruses express non-structural protein 1 (NS1), which is largely dedicated to antagonism of the host IFN response. This chapter describes how influenza viruses induce the IFN response and the ample means they have developed to intersect with it at all three stages of the pathway. The molecular details of NS1-mediated IFN antagonism are discussed, as well as new vaccination and antiviral drug strategies that target NS1 to attenuate virus replication.

Further reading: Viruses and Interferon: Current Research

from Maudry Laurent-Rolle, Juliet Morrison and Adolfo García-Sastre writing in Molecular Virology and Control of Flaviviruses:

Flaviviruses, along with the distantly related Hepacivirus and Pestiviruses, belong to the Flaviviridae family. Currently, more than 70 flaviviruses have been reported, including dengue virus serotypes 1 to 4 (DENV1-4), yellow fever virus (YFV), West Nile virus (WNV), Japanese encephalitis virus (JEV) and tick-borne encephalitis virus (TBEV). Flaviviruses are significant human and animal pathogens, creating a global public health challenge with more than 100 million people infected yearly. Typical manifestations of flaviviral disease in humans include jaundice, an acute febrile illness, hemorrhagic disease, encephalitis, and even death. Currently, there are no specific antiviral treatments for infection with any of the flaviviruses. An understanding of the interplay between the virus and the host immune system would aid in the development of flaviviral therapeutics. The innate immune system is the host's first line of defense against invading pathogens. Critical components of the innate immune system include natural killer (NK) cells, the complement system, and the ability to recognize pathogens like viruses and induce antiviral cytokines. These components of the innate immune system play complementary roles in limiting viral replication and dissemination, as well as initiation of the adaptive immune response. While all flaviviruses examined thus far suppress host innate immune responses to viral infection, the mechanisms by which this occurs differ among viruses. In this chapter, we will examine the roles that the different arms of the innate immune system play in protecting the host against flavivirus infection. We will also discuss the mechanisms that flaviviruses use to subvert the innate immune system and establish infection.

Further reading: Molecular Virology and Control of Flaviviruses

from Julien Lescar, Siew Pheng Lim and Pei-Yong Shi writing in Molecular Virology and Control of Flaviviruses:

The non-structural protein 5 (NS5) of flaviviruses is the most conserved amongst the viral proteins. It is about 900 kDa and bears several enzymatic activities that play vital roles in virus replication. Its N-terminal domain encodes dual N7 and 2'-O methyltransferase activities (MTase), and possibly guanylyltransferase (GTase) involved in RNA cap formation. The C-terminal region comprises a RNA-dependent RNA polymerase (RdRp) required for viral RNA synthesis. Numerous crystal structures of the Flavivirus MTase and RdRp domains have been solved. MTase in complex with S-adenosyl homocysteine (SAHC) or GTP analogues showed that the domain adopts a classical 2'-O MTase fold, however, the mechanism by which the protein can perform N7-methylation is still unknown. Besides its critical enzymatic activities, NS5 has also been implicated in viral pathogenesis through phosphorylation by host cell kinases, nucleus trafficking, and interference with interferon signalling and cytokine production. Here we summarize recent progress on this highly intriguing protein.

Further reading: Molecular Virology and Control of Flaviviruses

from Dahai Luoa, Siew Pheng Lim and Julien Lescar writing in Molecular Virology and Control of Flaviviruses:

The non-structural protein 3 (NS3) of flaviviruses is the second most conserved amongst the viral proteins. It bears a molecular mass of 69 kDa and is endowed with multiple functions including proteolytic processing, nucleic acid duplexes unwinding, nucleoside triphosphatase (NTPase) and RNA nucleoside 5' triphosphatase (RTPase). Besides these enzymatic activities which are essential for replication of viral genomic RNA, this protein also participates in other aspects of the viral life cycle. Numerous crystal structures of apo- and ligand-bound 3D structures for the protease and helicase domains of NS3, as well as for the full-length NS3 polypeptide (NS3FL) have been determined, providing insight at the atomic level into its various enzymatic activities. In this chapter, we summarize recent progress published regarding the function and structure of this fascinating viral non-structural protein including its recently uncovered dynamic properties.

Further reading: Molecular Virology and Control of Flaviviruses

from David Muller and Paul R Young writing in Molecular Virology and Control of Flaviviruses:

The Flavivirus non-structural protein, NS1 is an enigmatic protein whose structure and mechanistic function has remained elusive since it was first identified in 1970 as a viral antigen circulating in the sera of dengue infected patients. All Flavivirus NS1 genes share a high degree of homology, encoding a 352 amino acid polypeptide that has a molecular weight of between 46 and 55 kDa depending on its glycosylation status. NS1 exists in multiple oligomeric forms and is found at different cellular locations; cell membrane associated in vesicular compartments within the cell or on the cell surface and as a secreted extracellular hexamer. Intracellular NS1 plays an essential cofactor role in virus replication and has been shown to co-localize with dsRNA and other components of the viral replication complex. However the precise function of this protein in viral replication has yet to be elucidated. Secreted and cell surface associated NS1 are highly immunogenic and either the protein or the antibodies it elicits have been implicated in both protection and pathogenesis in infected hosts. It is also an important biomarker for early diagnosis. In this review we provide an overview of these disparate areas of research.

Further reading: Molecular Virology and Control of Flaviviruses

from Lee-Ching Ng and Indra Vythilingam writing in Molecular Virology and Control of Flaviviruses:

Recent worsening of global dengue situation, geographical spread of the West Nile virus to the United States and the unexpected emergence of the Zika virus on the Yap island in the Pacific, have placed mosquito-borne flaviviruses in the limelight. Vector control remains as a key measure for prevention and control of these diseases. Mosquito borne flaviviruses are vectored by an array of mosquito species, with different behaviour and habitats. This chapter discusses the principles of vector control using Singapore's dengue control programme to illustrate a strategy for urban peridomestic Aedes mosquitoes; and control of rural WNV and JEV to demonstrate strategies for rural Culex mosquitoes. In both situations, the incorporation of measures that consider the complex interplay of factors, including disease ecology, vector bionomics, land use, human activities and other social economic development, is essential. Despite the different strategies demanded by different vectors of diverse ecology and bionomics, the organisational framework that guide vector control remains consistent. The management system demands cost-effectiveness, which seeks synergies among the various tools used, and among various stakeholders. Sustainability, insecticide resistance and negative impact on the environment remain as some of the challenges faced by vector control programmes.

Further reading: Molecular Virology and Control of Flaviviruses

from Ben X. Wang, Ramtin Rahbar and Eleanor N. Fish writing in Viruses and Interferon: Current Research:

In this chapter, the clinical uses of interferons (IFNs), predominantly the IFN-αs, will be reviewed in the context of virus infections and neoplasias. The last 30 years have seen an accumulation of clinical studies evaluating the potential safety and efficacy of IFN treatment for acute and chronic virus infections, most notably hepatitis C virus. Moreover, given the pleiotropic effects of type I IFNs in terms of their antiproliferative and apoptotic effects, their anti-angiogenic effects and their ability to modulate an immune response specifically activating dendritic cells, cytolytic T cells and NK cells, their therapeutic potential for the treatment of a wide variety of leukemias and solid tumors has received intensive investigation.

Further reading: Viruses and Interferon: Current Research

from Michael S. Diamond, Theodore C. Pierson, and John T. Roehrig writing in Molecular Virology and Control of Flaviviruses:

Flaviviruses are a group of small RNA enveloped viruses that cause severe disease in humans worldwide. Recent advances in the structural biology of the flavivirus envelope proteins and virion have catalyzed rapid progress toward understanding how the most potently inhibitory antibodies neutralize infection. These insights have identified factors that modulate the potency of neutralizing antibodies and provided insight into the design of novel antibody-based therapeutics against several members of the flavivirus genus. This chapter will discuss recent advances in the understanding of the mechanisms of antibody neutralization of flaviviruses, and review the progress towards development of antibody-based therapeutics against several different flaviviruses of global concern.

Further reading: Molecular Virology and Control of Flaviviruses

from Beatriz Perdiguero and Mariano Esteban writing in Viruses and Interferon: Current Research:

Since the discovery of interferons (IFNs) more than half a century ago, these molecules have become key players of many cellular processes, particularly in the control of viral infections, cell growth and immune regulation. How the cells respond to IFN and identification of the molecular signals involved is a major goal in research. In this chapter we address these issues through the current understanding of the interaction between poxviruses and the IFN system. These large DNA containing viruses have acquired during their evolution an array of genes that counteract the IFN pathways at multiple levels. How the viral genes act is presented.

Further reading: Viruses and Interferon: Current Research

from Stephanie J. DeWitte-Orr and Karen L. Mossman writing in Viruses and Interferon: Current Research:

Viral double-stranded RNA (dsRNA), a replication by-product of almost all viruses, has been studied for over 55 years, first as a toxin, then as a type I IFN inducer, a viral mimetic and an immunomodulator for therapeutic purposes. Not only does dsRNA function as a pathogen associated molecular pattern (PAMP), sensed by host germline encoded pattern recognition receptors (PRRs) to stimulate innate immune responses, it also acts as a bridge to activate antiviral adaptive immune responses. DsRNA is generated intracellularly during a virus infection, but is released into the extracellular space during cell lysis. This review will focus on the structure and generation (both endogenous and viral) of extracellular dsRNA, and the host sensing mechanisms that result in type I IFN- and RNAi-mediated antiviral responses. The possible therapeutic applications of these findings will also be discussed. The goal of this review is to highlight the importance of this unique nucleic acid, with a focus on how its extracellularity influences its effects on the host and how these effects can be manipulated for our therapeutic purposes.

Further reading: Viruses and Interferon: Current Research

from Kazuhide Onoguchi, Kiyohiro Takahasi, Mitsutoshi Yoneyama, and Takashi Fujita writing in Viruses and Interferon: Current Research:

Type I interferon (IFN) is produced in variety of tissues in the body. It has been known that viral infection efficiently induces type I IFN. Bacterial endotoxin and double stranded (ds) RNA are representative non-viral inducers. Recent works revealed that cellular receptors for Pathogen Associated Molecular Patterns (PAMPs) are responsible for triggering IFN production. In the case of virus infection, RNA molecules encoded by viruses are sensed by the PAMPs receptors. Different viruses preferentially activate different sensor molecules. Current knowledge on virus- or RNA pathogen-specificity as well as structure-function relationship of RNA sensing is summarized. Furthermore, numerous signaling adaptors are reported to participate in the regulation of IFN gene activation.

Further reading: Viruses and Interferon: Current Research

from Srikanth Chiliveru and Søren R. Paludan writing in Viruses and Interferon: Current Research:

Virus infections stimulate host immune responses characterized by production of interferons (IFNs). The identification of IFN-λ (alternatively termed interleukin 28A/B, -29 or type III IFNs) has revealed that the immune response to viruses has more components than the type I IFNs known for more than 50 years. IFN-λs are known to have type-I-IFN-like biological activities, but our understanding of these novel players in the antiviral response is still under development. In this chapter, we describe the current knowledge on expression and function of type III IFNs in innate antiviral immune defenses and discuss recent findings proposing IFN-λ to shape the adaptive immune response. We suggest that type III IFNs are key antiviral cytokines exerting direct antiviral functions at epithelial surfaces at the early stages of infection, and that this class of cytokines also promotes antigen-specific cytotoxic activity of CD8+ T lymphocytes at later stages of the antiviral immune response.

Further reading: Viruses and Interferon: Current Research

from Marisela Rodriguez, Jessica A. Campbell and Deborah J. Lenschow writing in Viruses and Interferon: Current Research:

The type I interferon (IFN) system plays a critical role in limiting the spread of viral infection. Viruses induce the production of IFN-α and ¹Äìβ, which bind to the IFN-α/ β receptor (IFNAR) and trigger the JAK/STAT signaling cascade. The ensuing induction of IFN-stimulated genes (ISGs) inhibits viral replication by targeting multiple points in the viral life cycle. ISGs exert their antiviral function through diverse mechanisms, including activities directly targeting the virus such as the degradation of viral RNA, the inhibition of translation, the blockade of virion release, and actions that modify the host response including regulation of the IFN response, NF-κB signaling, and apoptosis, among others. This chapter reviews several ISGs that have been shown to mediate antiviral activity either in vitro or in vivo, and in some cases, both. The mechanisms by which individual ISGs confer cellular protection are summarized, although the effector pathways of certain ISGs are still being delineated. The study of ISGs continues to provide important contributions to our understanding of the host-virus interface and the cellular antiviral response.

Further reading: Viruses and Interferon: Current Research