Bunyamwera Bunyavirus Nonstructural Protein NSs Counteracts the Induction of Alpha/beta Interferon

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2002 Jul 23

PMID 12133999

Citations 112

Authors

Friedemann Weber

Anne Bridgen

John K Fazakerley

Hein Streitenfeld

Nina Kessler

Richard E Randall

Richard M Elliott

Affiliations

Soon will be listed here.

Abstract

Production of alpha/beta interferons (IFN-alpha/beta) in response to viral infection is one of the main defense mechanisms of the innate immune system. Many viruses therefore encode factors that subvert the IFN system to enhance their virulence. Bunyamwera virus (BUN) is the prototype of the Bunyaviridae family. By using reverse genetics, we previously produced a recombinant virus lacking the nonstructural protein NSs (BUNdelNSs) and showed that NSs is a nonessential gene product that contributes to viral pathogenesis. Here we demonstrate that BUNdelNSs is a strong inducer of IFN-alpha/beta, whereas in cells infected with the wild-type counterpart expressing NSs (wild-type BUN), neither IFN nor IFN mRNA could be detected. IFN induction by BUNdelNSs correlated with activation of NF-kappaB and was dependent on virally produced double-stranded RNA and on the IFN transcription factor IRF-3. Furthermore, both in cultured cells and in mice lacking a functional IFN-alpha/beta system, BUNdelNSs replicated to wild-type BUN levels, whereas in IFN-competent systems, wild-type BUN grew more efficiently. These results suggest that BUN NSs is an IFN induction antagonist that blocks the transcriptional activation of IFN-alpha/beta in order to increase the virulence of Bunyamwera virus.

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References

Erlandsson L, Blumenthal R, Eloranta M, Engel H, Alm G, Weiss S . Interferon-beta is required for interferon-alpha production in mouse fibroblasts. Curr Biol. 1998; 8(4):223-6. DOI: 10.1016/s0960-9822(98)70086-7. View

Weaver B, Kumar K, Reich N . Interferon regulatory factor 3 and CREB-binding protein/p300 are subunits of double-stranded RNA-activated transcription factor DRAF1. Mol Cell Biol. 1998; 18(3):1359-68. PMC: 108849. DOI: 10.1128/MCB.18.3.1359. View

Lin R, Heylbroeck C, Pitha P, Hiscott J . Virus-dependent phosphorylation of the IRF-3 transcription factor regulates nuclear translocation, transactivation potential, and proteasome-mediated degradation. Mol Cell Biol. 1998; 18(5):2986-96. PMC: 110678. DOI: 10.1128/MCB.18.5.2986. View

Egorov A, Brandt S, Sereinig S, Romanova J, Ferko B, Katinger D . Transfectant influenza A viruses with long deletions in the NS1 protein grow efficiently in Vero cells. J Virol. 1998; 72(8):6437-41. PMC: 109801. DOI: 10.1128/JVI.72.8.6437-6441.1998. View

Wathelet M, Lin C, Parekh B, Ronco L, Howley P, Maniatis T . Virus infection induces the assembly of coordinately activated transcription factors on the IFN-beta enhancer in vivo. Mol Cell. 1998; 1(4):507-18. DOI: 10.1016/s1097-2765(00)80051-9. View

Jacobs B, Langland J, Brandt T . Characterization of viral double-stranded RNA-binding proteins. Methods. 1998; 15(3):225-32. DOI: 10.1006/meth.1998.0626. View

Stark G, Kerr I, Williams B, Silverman R, Schreiber R . How cells respond to interferons. Annu Rev Biochem. 1998; 67:227-64. DOI: 10.1146/annurev.biochem.67.1.227. View

Feigenblum D, Walker R, Schneider R . Adenovirus induction of an interferon-regulatory factor during entry into the late phase of infection. J Virol. 1998; 72(11):9257-66. PMC: 110345. DOI: 10.1128/JVI.72.11.9257-9266.1998. View

Marie I, Durbin J, Levy D . Differential viral induction of distinct interferon-alpha genes by positive feedback through interferon regulatory factor-7. EMBO J. 1998; 17(22):6660-9. PMC: 1171011. DOI: 10.1093/emboj/17.22.6660. View

10.

Garcia-Sastre A, Egorov A, Matassov D, Brandt S, Levy D, Durbin J . Influenza A virus lacking the NS1 gene replicates in interferon-deficient systems. Virology. 1999; 252(2):324-30. DOI: 10.1006/viro.1998.9508. View

11.

Conzelmann K . Nonsegmented negative-strand RNA viruses: genetics and manipulation of viral genomes. Annu Rev Genet. 1999; 32:123-62. DOI: 10.1146/annurev.genet.32.1.123. View

12.

Michiels T . Absence of internal ribosome entry site-mediated tissue specificity in the translation of a bicistronic transgene. J Virol. 1999; 73(4):2729-38. PMC: 104029. DOI: 10.1128/JVI.73.4.2729-2738.1999. View

13.

Didcock L, Young D, Goodbourn S, Randall R . The V protein of simian virus 5 inhibits interferon signalling by targeting STAT1 for proteasome-mediated degradation. J Virol. 1999; 73(12):9928-33. PMC: 113042. DOI: 10.1128/JVI.73.12.9928-9933.1999. View

14.

Chu W, Ostertag D, Li Z, Chang L, Chen Y, Hu Y . JNK2 and IKKbeta are required for activating the innate response to viral infection. Immunity. 2000; 11(6):721-31. DOI: 10.1016/s1074-7613(00)80146-6. View

15.

Didcock L, Young D, Goodbourn S, Randall R . Sendai virus and simian virus 5 block activation of interferon-responsive genes: importance for virus pathogenesis. J Virol. 1999; 73(4):3125-33. PMC: 104074. DOI: 10.1128/JVI.73.4.3125-3133.1999. View

16.

Neumann G, Watanabe T, Ito H, Watanabe S, Goto H, Gao P . Generation of influenza A viruses entirely from cloned cDNAs. Proc Natl Acad Sci U S A. 1999; 96(16):9345-50. PMC: 17785. DOI: 10.1073/pnas.96.16.9345. View

17.

Zhang J, Yamada O, Ito T, Akiyama M, Hashimoto Y, Yoshida H . A single nucleotide insertion in the 5'-untranslated region of hepatitis C virus leads to enhanced cap-independent translation. Virology. 1999; 261(2):263-70. DOI: 10.1006/viro.1999.9879. View

18.

Mogensen T, DiDonato J, Williams B . NF-kappaB activation by double-stranded-RNA-activated protein kinase (PKR) is mediated through NF-kappaB-inducing kinase and IkappaB kinase. Mol Cell Biol. 2000; 20(4):1278-90. PMC: 85265. DOI: 10.1128/MCB.20.4.1278-1290.2000. View

19.

Deonarain R, Alcami A, Alexiou M, Dallman M, Gewert D, Porter A . Impaired antiviral response and alpha/beta interferon induction in mice lacking beta interferon. J Virol. 2000; 74(7):3404-9. PMC: 111842. DOI: 10.1128/jvi.74.7.3404-3409.2000. View

20.

Young D, Didcock L, Goodbourn S, Randall R . Paramyxoviridae use distinct virus-specific mechanisms to circumvent the interferon response. Virology. 2001; 269(2):383-90. DOI: 10.1006/viro.2000.0240. View