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Archives of Virology

, Volume 159, Issue 7, pp 1735–1741 | Cite as

Physical interaction between bovine viral diarrhea virus nonstructural protein 4A and adenosine deaminase acting on RNA (ADAR)

  • Yassir Mahgoub Mohamed
  • Norasuthi Bangphoomi
  • Daisuke Yamane
  • Yuto Suda
  • Kentaro Kato
  • Taisuke Horimoto
  • Hiroomi AkashiEmail author
Original Article

Abstract

Bovine viral diarrhea virus (BVDV) is a positive-sense RNA virus known to produce double-stranded RNA (dsRNA) during its replication in the cytoplasm. Extended dsRNA duplexes can be hyperedited by adenosine deaminase acting on RNA (ADAR), which catalyzes adenosine (A)-to-inosine (I) editing. A-to-I editing has been reported for various viruses. A number of cellular antiviral defense strategies are stimulated by dsRNA, and this may involve hyperediting of dsRNA by ADARs, followed by targeted cleavage by cytoplasmic endonucleases. Here, we identify ADAR as a binding partner of BVDV NS4A in vitro and in vivo and show that the N-terminal domain of NS4A is the ADAR-binding domain. We also show that ADAR has an inhibitory effect on BVDV replication when overexpressed in BVDV-infected bovine cells. Our findings suggest a role of NS4A in the interaction of BVDV with ADAR that favors virus replication.

Keywords

Bovine Viral Diarrhea Virus Bovine Viral Diarrhea Virus Infection Subgenomic Replicon Bovine Viral Diarrhea Virus Strain NS4A Sequence 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

We thank Dr. Till Rümenapf and Dr. Graeme Conn for providing research materials. This work was supported in part by a Research and Development Project for Application in Promoting New Policies in Agriculture, Forestry and Fisheries grant from the Ministry of Agriculture, Forestry and Fisheries, and by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology, Japan.

References

  1. 1.
    Adler B, Adler H, Pfister H, Jungi TW, Peterhans E (1997) Macrophages infected with cytopathic bovine viral diarrhea virus release a factor(s) capable of priming uninfected macrophages for activation-induced apoptosis. J Virol 71:3255–3258PubMedCentralPubMedGoogle Scholar
  2. 2.
    Basilio C, Wahba AJ, Lengyel P, Speyer JF, Ochoa S (1962) Synthetic polynucleotides and the amino acid code. V. Proc Natl Acad Sci USA 48:613–616PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Bass BL, Weintraub H, Cattaneo R, Billeter MA (1989) Biased hypermutation of viral RNA genomes could be due to unwinding/modification of double-stranded RNA. Cell 56:331PubMedCrossRefGoogle Scholar
  4. 4.
    Bass BL, Nishikura K, Keller W, Seeburg PH, Emeson RB, O’Connell MA, Samuel CE, Herbert A (1997) A standardized nomenclature for adenosine deaminases that act on RNA. RNA 3:947–949PubMedCentralPubMedGoogle Scholar
  5. 5.
    Cattaneo R, Schmid A, Eschle D, Baczko K, ter Meulen V, Billeter MA (1988) Biased hypermutation and other genetic changes in defective measles viruses in human brain infections. Cell 55:255–265PubMedCrossRefGoogle Scholar
  6. 6.
    Cattaneo R, Schmid A, Spielhofer P, Kaelin K, Baczko K, ter Meulen V, Pardowitz J, Flanagan S, Rima BK, Udem SA et al (1989) Mutated and hypermutated genes of persistent measles viruses which caused lethal human brain diseases. Virology 173:415–425PubMedCrossRefGoogle Scholar
  7. 7.
    Gerber AP, Keller W (2001) RNA editing by base deamination: more enzymes, more targets, new mysteries. Trends Biochem Sci 26:376–384PubMedCrossRefGoogle Scholar
  8. 8.
    Gott JM, Emeson RB (2000) Functions and mechanisms of RNA editing. Annu Rev Genet 34:499–531PubMedCrossRefGoogle Scholar
  9. 9.
    Lei M, Liu Y, Samuel CE (1998) Adenovirus VAI RNA antagonizes the RNA-editing activity of the ADAR adenosine deaminase. Virology 245:188–196PubMedCrossRefGoogle Scholar
  10. 10.
    Nagai M, Sakoda Y, Mori M, Hayashi M, Kida H, Akashi H (2003) Insertion of cellular sequence and RNA recombination in the structural protein coding region of cytopathogenic bovine viral diarrhoea virus. J Gen Virol 84:447–452PubMedCrossRefGoogle Scholar
  11. 11.
    Ngamurulert S, Limjindaporn T, Auewaraku P (2009) Identification of cellular partners of Influenza A virus (H5N1) non-structural protein NS1 by yeast two-hybrid system. Acta Virologica 53:153–159PubMedCrossRefGoogle Scholar
  12. 12.
    Perler L, Schweizer M, Jungi TW, Peterhans E (2000) Bovine viral diarrhoea virus and bovine herpesvirus-1 prime uninfected macrophages for lipopolysaccharide-triggered apoptosis by interferon-dependent and -independent pathways. J Gen Virol 81:881–887PubMedGoogle Scholar
  13. 13.
    Samuel CE (2011) Adenosine deaminases acting on RNA (ADARs) are both antiviral and proviral. Virology 411:180–193PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Scadden AD, Smith CW (2001) Specific cleavage of hyper-edited dsRNAs. EMBO J 20:4243–4252PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Schagger H (2006) Tricine-SDS-PAGE. Nat Protoc 1:16–22PubMedCrossRefGoogle Scholar
  16. 16.
    Taylor DR, Puig M, Darnell ME, Mihalik K, Feinstone SM (2005) New antiviral pathway that mediates hepatitis C virus replicon interferon sensitivity through ADAR1. J Virol 79:6291–6298PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Wahid AM, Coventry VK, Conn GL (2009) The PKR-binding domain of adenovirus VA RNAI exists as a mixture of two functionally non-equivalent structures. Nucleic Acids Res 37:5830–5837PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Yamane D, Nagai M, Ogawa Y, Tohya Y, Akashi H (2005) Enhancement of apoptosis via an extrinsic factor, TNF-alpha, in cells infected with cytopathic bovine viral diarrhea virus. Microbes Infect 7:1482–1491PubMedCrossRefGoogle Scholar
  19. 19.
    Yamane D, Kato K, Tohya Y, Akashi H (2008) The relationship between the viral RNA level and upregulation of innate immunity in spleen of cattle persistently infected with bovine viral diarrhea virus. Vet Microbiol 129:69–79PubMedCrossRefGoogle Scholar
  20. 20.
    Yamane D, Zahoor MA, Mohamed YM, Azab W, Kato K, Tohya Y, Akashi H (2009) Microarray analysis reveals distinct signaling pathways transcriptionally activated by infection with bovine viral diarrhea virus in different cell types. Virus Res 142:188–199PubMedCrossRefGoogle Scholar
  21. 21.
    Yamane D, Zahoor MA, Mohamed YM, Azab W, Kato K, Tohya Y, Akashi H (2009) Inhibition of sphingosine kinase by bovine viral diarrhea virus NS3 is crucial for efficient viral replication and cytopathogenesis. J Biol Chem 284:13648–13659PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 2014

Authors and Affiliations

  • Yassir Mahgoub Mohamed
    • 1
    • 2
  • Norasuthi Bangphoomi
    • 2
  • Daisuke Yamane
    • 2
  • Yuto Suda
    • 2
  • Kentaro Kato
    • 2
  • Taisuke Horimoto
    • 2
  • Hiroomi Akashi
    • 2
    Email author
  1. 1.Department of Microbiology, Tropical Medicine Research InstituteNational Centre for ResearchKhartoumSudan
  2. 2.Department of Veterinary Microbiology, Graduate School of Agricultural and Life SciencesThe University of TokyoTokyoJapan

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