Rhabdoviruses and Mechanisms of Type I Interferon Antagonism

Krzysztof Brzózka; Karl-Klaus Conzelmann

doi:10.1128/9781555815561.ch14

Chapter 14 : Rhabdoviruses and Mechanisms of Type I Interferon Antagonism

Authors: Krzysztof Brzózka¹, Karl-Klaus Conzelmann²

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Affiliations: 1: Max von Pettenkofer Institute & Gene Center, Ludwig-Maximilians-University Munich, Feodor-Lynen-Str. 25, 81377 Munich, Germany; 2: Max von Pettenkofer Institute & Gene Center, Ludwig-Maximilians-University Munich, Feodor-Lynen-Str. 25, 81377 Munich, Germany

Content Type: Monograph

Publication Year: 2009

Category: Viruses and Viral Pathogenesis; Microbial Genetics and Molecular Biology

Book DOI: 10.1128/9781555815561

Chapter DOI: 10.1128/9781555815561.ch14

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Abstract:

The Novirhabdovirus genus includes typical rhabdoviruses from fish, such as viral hemorrhagic septicemia virus, which infects numerous marine and freshwater fish species. Rhabdoviruses that infect plants are separated into the genera Cytorhabdovirus and Nucleorhabdovirus, based on their sites of replication and morphogenesis. The leader RNA of rhabdoviruses is the prime target candidate for recognition by retinoic acid-inducible gene I (RIG-I). Defective interfering (DI) particle RNAs are generated notoriously in fast-replicating rhabdoviruses like vesicular stomatitis virus (VSV). Rhabdoviruses are being recognized by nucleic acid pattern receptors, although most of their RNA is shielded by N protein, and at the latest when they start gene expression by synthesis of leader RNA. The crucial point is therefore to limit the consequential interferon (IFN) production and the expression of IFN-stimulated genes (ISGs) as long and as far as possible by expression of “IFN antagonists.” This chapter analyzes the rhabdoviruses with respect to type I IFN antagonism. Characterization of the mechanisms involved in IFN escape of rhabdoviruses will help to better explain how self and nonself are distinguished and how host signaling networks are connected and regulated and how they function. Furthermore, studies on rhabdoviruses like VSV in its vector host, and of other rhabdoviruses of fish, insects, and plants, will undoubtedly provide further intriguing insights into the host defense mechanisms and the intricate relationship with viruses.

Citation: Brzózka K, Conzelmann K. 2009. Rhabdoviruses and Mechanisms of Type I Interferon Antagonism, p 211-227. In Brasier A, García-Sastre A, Lemon S (ed), Cellular Signaling and Innate Immune Responses to RNA Virus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555815561.ch14

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Rhabdoviruses and Mechanisms of Type I Interferon Antagonism

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Figure 1

Transcription and replication products of rhabdoviruses. The full-length triphosphate genome and antigenome RNAs are present exclusively in an NC RNP. The genome NC is the template for production of a short triphosphate leader RNA and sequential transcription of five monocistronic capped and polyadenylated mRNAs. Since the polymerase complex P/L eventually dissociates from the template, a transcription gradient is generated. Replicative synthesis of full-length antigenomes involves concurrent packaging by N/P complexes into an NC.

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Figure 1

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Figure 2

IFN antagonists of RV and VSV. Rhabdovirus triphosphate RNAs are recognized by RIG-I, resulting in association of the CARD domains of RIG-I and IPS-1 and recruitment of a complex in which IRF3 is phosphorylated by TBK1. Phosphorylation results in dimerization of IRF3, import into the nucleus, and transcriptional activation of the IFN-β gene. In the presence of RV P, IRF3 phosphorylation is prevented. RV P binds also to phosphorylated Stat1 and Stat2, preventing expression of ISGs after IFN stimulation of the IFN receptor (IFNAR). VSV M causes a shutdown of Pol II transcription, thereby preventing transcription of both IFN genes and ISGs. In addition, VSV M interferes with the nuclear export of mRNAs by blocking Nup98 (see text for details).

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