Processing of genome 5' termini as a strategy of negative-strand RNA viruses to avoid RIG-I-dependent interferon induction

• Published in: PloS one 2008-04, Vol.3 (4), p.e2032-e2032
• Main Authors: Habjan, Matthias, Andersson, Ida, Klingström, Jonas, Schümann, Michael, Martin, Arnold, Zimmermann, Petra, Wagner, Valentina, Pichlmair, Andreas, Schneider, Urs, Mühlberger, Elke, Mirazimi, Ali, Weber, Friedemann
• Format: Article
• Language: English
• Subjects: Acids; Biological response modifiers; Biology; Borna disease; Cell Line; Coccidioidomycosis; Crimean hemorrhagic fever; Cytokines; DEAD Box Protein 58; DEAD-box RNA Helicases - immunology; Disease control; Ebola virus; Ebolavirus; Exonuclease; Fever; Genes; Genome, Viral - genetics; Genomes; Genomics; Hemorrhage; Hemorrhagic fevers; Humans; Immune response; Immune system; Immunity; Immunology/Immunomodulation; Immunology/Innate Immunity; Infections; Infectious diseases; Infectious Diseases/Viral Infections; Influenza; Innate immunity; Interferon; Interferons - immunology; Intracellular; Measles; Medical research; Medicin och hälsovetenskap; Microbiology; Nipah virus; Pathogens; Pattern recognition; Phosphatases; Phosphates; Post-transcription; Rabies; Receptors; Receptors, Immunologic; Recognition; Respiratory syncytial virus; Ribonucleic acid; Rift Valley fever; RNA; RNA viruses; RNA Viruses - genetics; RNA Viruses - pathogenicity; RNA, Viral - genetics; Transcription; Transcription factors; Vector-borne diseases; Viral diseases; Virology; Virology/Effects of Virus Infection on Host Gene Expression; Virology/Emerging Viral Diseases; Virology/Host Antiviral Responses; Virology/Immune Evasion; Virology/Persistence and Latency; Virulence; Viruses; β-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0002032

Innate immunity is critically dependent on the rapid production of interferon in response to intruding viruses. The intracellular pathogen recognition receptors RIG-I and MDA5 are essential for interferon induction by viral RNAs containing 5' triphosphates or double-stranded structures, respectively. Viruses with a negative-stranded RNA genome are an important group of pathogens causing emerging and re-emerging diseases. We investigated the ability of genomic RNAs from substantial representatives of this virus group to induce interferon via RIG-I or MDA5. RNAs isolated from particles of Ebola virus, Nipah virus, Lassa virus, and Rift Valley fever virus strongly activated the interferon-beta promoter. Knockdown experiments demonstrated that interferon induction depended on RIG-I, but not MDA5, and phosphatase treatment revealed a requirement for the RNA 5' triphosphate group. In contrast, genomic RNAs of Hantaan virus, Crimean-Congo hemorrhagic fever virus and Borna disease virus did not trigger interferon induction. Sensitivity of these RNAs to a 5' monophosphate-specific exonuclease indicates that the RIG-I-activating 5' triphosphate group was removed post-transcriptionally by a viral function. Consequently, RIG-I is unable to bind the RNAs of Hantaan virus, Crimean-Congo hemorrhagic fever virus and Borna disease virus. These results establish RIG-I as a major intracellular recognition receptor for the genome of most negative-strand RNA viruses and define the cleavage of triphosphates at the RNA 5' end as a strategy of viruses to evade the innate immune response.