Skip to main content

Advertisement

SpringerLink
Log in

The Vif protein of caprine arthritis encephalitis virus inhibits interferon production

  • Original Article
  • Published:
Archives of Virology Aims and scope Submit manuscript

Abstract

Caprine arthritis-encephalitis (CAE) is a chronic progressive infectious disease caused by caprine arthritis-encephalitis virus (CAEV) that seriously threatens the goat industry. Chronic infection and life-long multi-tissue inflammation are the typical features of the disease. Innate antiviral immunity is essential for the host defense system that rapidly recognizes and eliminates invading viruses. Interferon β (IFN-β) is important for innate immunity and regulates immunity against a broad spectrum of viruses. To investigate the details of the IFN-β response to CAEV infection, the effects of six viral proteins and the molecular mechanisms by which they affect IFN-β production were analyzed. Overexpression of DU and Vif promote virus proliferation and inhibit the production of IFN-β. qRT-PCR and luciferase reporter assays showed that overexpression of Vif inhibits the expression of luciferase under the control of the ISRE, NF-κB or IFN-β promoter but does not affect the expression of IFN-β activated by IRF3, indicating that Vif negatively regulates IFN-β production by affecting upstream signal transduction of IRF3. Amino acids 149-164 of Vif were found to be necessary for the inhibitory effect of IFN-β production. Our results indicate that CAEV evades surveillance and clearance by intracellular innate immunity by downregulating IFN-β production.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. O’Sullivan BM, Eaves FW, Baxendell SA, Rowan KJ (1978) Leucoencephalomyelitis of goat kids. Aust Vet J 54:479–483

    Article  PubMed  Google Scholar 

  2. Adams DS, Crawford TB, Klevjer-Anderson P (1980) A pathogenetic study of the early connective tissue lesions of viral caprine arthritis–encephalitis. Am J Pathol 99:257–278

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Crawford TB, Adams DS, Cheevers WP, Cork LC (1980) Chronic arthritis in goats caused by a retrovirus. Science 207:997–999

    Article  CAS  PubMed  Google Scholar 

  4. Lamara A, Fieni F, Chatagnon G, Larrat M, Dubreil L, Chebloune Y (2013) Caprine arthritis encephalitis virus (CAEV) replicates productively in cultured epididymal cells from goats. Comp Immunol Microbiol Infect Dis 36:397–404

    Article  PubMed  Google Scholar 

  5. Li Y, Zhou F, Li X, Wang J, Zhao X, Huang J (2013) Development of TaqMan-based qPCR method for detection of caprine arthritis-encephalitis virus (CAEV) infection. Arch Virol 158:2135–2141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Crawford TB, Adams DS (1981) Caprine arthritis–encephalitis: clinical features and presence of antibody in selected goat populations. J Am Vet Med Assoc 178:713–719

    CAS  PubMed  Google Scholar 

  7. Tageldin MH, Johnson EH, Al-Busaidi RM, Al-Habsi KR, Al-Habsi SS (2012) Serological evidence of caprine arthritis-encephalitis virus (CAEV) infection in indigenous goats in the Sultanate of Oman. Trop Anim Health Prod 44:1–3

    Article  PubMed  Google Scholar 

  8. Tu PA, Shiu JS, Lee SH, Pang VF, Wang DC, Wang PH (2017) Development of a recombinase polymerase amplification lateral flow dipstick (RPA-LFD) for the field diagnosis of caprine arthritis–encephalitis virus (CAEV) infection. J Virol Methods 243:98–104

    Article  CAS  PubMed  Google Scholar 

  9. Michiels R, Van Mael E, Quinet C, Welby S, Cay AB, De Regge N (2018) Seroprevalence and risk factors related to small ruminant lentivirus infections in Belgian sheep and goats. Prev Vet Med 151:13–20

    Article  PubMed  Google Scholar 

  10. Adedeji AO, Barr B, Gomez-Lucia E, Murphy B (2013) A polytropic caprine arthritis encephalitis virus promoter isolated from multiple tissues from a sheep with multisystemic lentivirus-associated inflammatory disease. Viruses 5:2005–2018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Hess JL, Pyper JM, Clements JE (1986) Nucleotide sequence and transcriptional activity of the caprine arthritis–encephalitis virus long terminal repeat. J Virol 60:385–393

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Barros SC, Andresdottir V, Fevereiro M (2005) Cellular specificity and replication rate of Maedi Visna virus in vitro can be controlled by LTR sequences. Arch Virol 150:201–213

    Article  CAS  PubMed  Google Scholar 

  13. Oskarsson T, Hreggvidsdottir HS, Agnarsdottir G, Matthiasdottir S, Ogmundsdottir MH, Jonsson SR, Georgsson G, Ingvarsson S, Andresson OS, Andresdottir V (2007) Duplicated sequence motif in the long terminal repeat of maedi-visna virus extends cell tropism and is associated with neurovirulence. J Virol 81:4052–4057

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. L’Homme Y, Leboeuf A, Arsenault J, Fras M (2015) Identification and characterization of an emerging small ruminant lentivirus circulating recombinant form (CRF). Virology 475:159–171

    Article  PubMed  CAS  Google Scholar 

  15. Valas S, Benoit C, Baudry C, Perrin G, Mamoun RZ (2000) Variability and immunogenicity of caprine arthritis–encephalitis virus surface glycoprotein. J Virol 74:6178–6185

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Harmache A, Russo P, Guiguen F, Vitu C, Vignoni M, Bouyac M, Hieblot C, Pepin M, Vigne R, Suzan M (1996) Requirement of caprine arthritis encephalitis virus vif gene for in vivo replication. Virology 224:246–255

    Article  CAS  PubMed  Google Scholar 

  17. Schoborg RV, Saltarelli MJ, Clements JE (1994) A Rev protein is expressed in caprine arthritis encephalitis virus (CAEV)-infected cells and is required for efficient viral replication. Virology 202:1–15

    Article  CAS  PubMed  Google Scholar 

  18. Korb J, Travnicek M, Riman J (1976) The oncornavirus maturation process: quantitative correlation between morphological changes and conversion of genomic virion RNA. Intervirology 7:211–224

    Article  CAS  PubMed  Google Scholar 

  19. Lamara A, Fieni F, Mselli-Lakhal L, Chatagnon G, Bruyas JF, Tainturier D, Battut I, Fornazero C, Chebloune Y (2002) Early embryonic cells from in vivo-produced goat embryos transmit the caprine arthritis-encephalitis virus (CAEV). Theriogenology 58:1153–1163

    Article  CAS  PubMed  Google Scholar 

  20. Lamara A, Fieni F, Mselli-Lakhal L, Tainturier D, Chebloune Y (2001) Efficient replication of caprine arthritis-encephalitis virus in goat granulosa cells. Virus Res 79:165–172

    Article  CAS  PubMed  Google Scholar 

  21. Cardinaux L, Zahno ML, Deubelbeiss M, Zanoni R, Vogt HR, Bertoni G (2013) Virological and phylogenetic characterization of attenuated small ruminant lentivirus isolates eluding efficient serological detection. Vet Microbiol 162:572–581

    Article  CAS  PubMed  Google Scholar 

  22. Blacklaws BA (2012) Small ruminant lentiviruses: immunopathogenesis of visna-maedi and caprine arthritis and encephalitis virus. Comp Immunol Microbiol Infect Dis 35:259–269

    Article  PubMed  Google Scholar 

  23. Jarczak J, Kaba J, Reczynska D, Bagnicka E (2016) Impaired expression of cytokines as a result of viral infections with an emphasis on small ruminant lentivirus infection in goats. Viruses 8(186):1–12

    Article  CAS  PubMed Central  Google Scholar 

  24. Medin CL, Rothman AL (2006) Cell type-specific mechanisms of interleukin-8 induction by dengue virus and differential response to drug treatment. J Infect Dis 193:1070–1077

    Article  CAS  PubMed  Google Scholar 

  25. Tanji T, Ip YT (2005) Regulators of the Toll and Imd pathways in the Drosophila innate immune response. Trends Immunol 26:193–198

    Article  CAS  PubMed  Google Scholar 

  26. Bourgeois C, Majer O, Frohner IE, Lesiak-Markowicz I, Hildering KS, Glaser W, Stockinger S, Decker T, Akira S, Muller M, Kuchler K (2011) Conventional dendritic cells mount a type I IFN response against Candida spp. requiring novel phagosomal TLR7-mediated IFN-beta signaling. J Immunol 186:3104–3112

    Article  CAS  PubMed  Google Scholar 

  27. Li J, Liu Y, Zhang X (2010) Murine coronavirus induces type I interferon in oligodendrocytes through recognition by RIG-I and MDA5. J Virol 84:6472–6482

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Meylan E, Tschopp J, Karin M (2006) Intracellular pattern recognition receptors in the host response. Nature 442:39–44

    Article  CAS  PubMed  Google Scholar 

  29. Belgnaoui SM, Paz S, Samuel S, Goulet ML, Sun Q, Kikkert M, Iwai K, Dikic I, Hiscott J, Lin R (2012) Linear ubiquitination of NEMO negatively regulates the interferon antiviral response through disruption of the MAVS–TRAF3 complex. Cell Host Microbe 12:211–222

    Article  CAS  PubMed  Google Scholar 

  30. Liu X, Wang Q, Pan Y, Wang C (2015) Sensing and responding to cytosolic viruses invasions: an orchestra of kaleidoscopic ubiquitinations. Cytokine Growth Factor Rev 26:379–387

    Article  CAS  PubMed  Google Scholar 

  31. Thanos D, Maniatis T (1995) Virus induction of human IFN beta gene expression requires the assembly of an enhanceosome. Cell 83:1091–1100

    Article  CAS  PubMed  Google Scholar 

  32. Shi P, Su Y, Li R, Liang Z, Dong S, Huang J (2019) PEDV nsp16 negatively regulates innate immunity to promote viral proliferation. Virus Res 265:57–66

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Cheevers WP, Beyer JC, Hotzel I (2001) Plasmid DNA encoding caprine interferon gamma inhibits antibody response to caprine arthritis-encephalitis virus (CAEV) surface protein encoded by a co-administered plasmid expressing CAEV env and tat genes. Vaccine 19:3209–3215

    Article  CAS  PubMed  Google Scholar 

  34. Hariya Y, Yokosawa N, Yonekura N, Kohama G, Fuji N (2013) Mumps virus can suppress the effective augmentation of HPC-induced apoptosis by IFN-gamma through disruption of IFN signaling in U937 cells. Microbiol Immunol 44:537–541

    Article  Google Scholar 

  35. Peng Q, Lan X, Wang C, Ren Y, Yue N, Wang J, Zhong B, Zhu Q (2017) Kobuvirus VP3 protein restricts the IFN-β-triggered signaling pathway by inhibiting STAT2–IRF9 and STAT2–STAT2 complex formation. Virology 507:161

    Article  CAS  PubMed  Google Scholar 

  36. Murphy B, Hillman C, Castillo D, Vapniarsky N, Rowe J (2012) The presence or absence of the gamma-activated site determines IFN gamma-mediated transcriptional activation in CAEV promoters cloned from the mammary gland and joint synovium of a single CAEV-infected goat. Virus Res 163:537–545

    Article  CAS  PubMed  Google Scholar 

  37. White-Ziegler CA, Low DA (1992) Thermoregulation of the pap operon: evidence for the involvement of RimJ, the N-terminal acetylase of ribosomal protein S5. J Bacteriol 174:7003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Turelli P, Guiguen F, Mornex JF, Vigne R, Querat G (1997) dUTPase-minus caprine arthritis-encephalitis virus is attenuated for pathogenesis and accumulates G-to-A substitutions. J Virol 71:4522–4530

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Carruth LM, Hardwick JM, Morse BA, Clements JE (1994) Visna virus Tat protein: a potent transcription factor with both activator and suppressor domains. J Virol 68:6137–6146

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Li R, Chen C, He J, Zhang L, Zhang L, Guo Y, Zhang W, Tan K, Huang J (2019) E3 ligase ASB8 promotes porcine reproductive and respiratory syndrome virus proliferation by stabilizing the viral Nsp1alpha protein and degrading host IKKbeta kinase. Virology 532:55–68

    Article  CAS  PubMed  Google Scholar 

  41. Shi P, Su Y, Li R, Zhang L, Chen C, Zhang L, Faaberg K, Huang J (2018) Dual regulation of host TRAIP post-translation and nuclear/plasma distribution by porcine reproductive and respiratory syndrome virus non-structural protein 1alpha promotes viral proliferation. Front Immunol 9:3023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Pulido MR, Sáiz M (2017) Molecular mechanisms of foot-and-mouth disease virus targeting the host antiviral response. Front Cell Infect Microbiol 7:252

    Article  CAS  Google Scholar 

  43. Zhang HL, Ye HQ, Liu SQ, Deng CL, Li XD, Shi PY, Zhang B (2017) West Nile virus NS1 antagonizes interferon-Î2 production by targeting RIG-I and MDA5. J Virol 91:JVI.02396-16

    Article  Google Scholar 

  44. Okumura A, Alce T, Lubyova B, Ezelle H, Strebel K, Pitha PM (2008) HIV-1 accessory proteins VPR and Vif modulate antiviral response by targeting IRF-3 for degradation. Virology 373:85–97

    Article  CAS  PubMed  Google Scholar 

  45. Park SY, Waheed AA, Zhang ZR, Freed EO, Bonifacino JS (2014) HIV-1 Vpu accessory protein induces caspase-mediated cleavage of IRF3 transcription factor. J Biol Chem 289:35102–35110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Bose D, Gagnon J, Chebloune Y (2015) Comparative analysis of tat-dependent and tat-deficient natural lentiviruses. Vet Sci 2:293–348

    Article  PubMed  PubMed Central  Google Scholar 

  47. Rathinam VA, Fitzgerald KA (2011) Cytosolic surveillance and antiviral immunity. Curr Opin Virol 1:455–462

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Killip MJ, Fodor E, Randall RE (2015) Influenza virus activation of the interferon system. Virus Res 209:11–22

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Harmache A, Bouyac M, Audoly G, Hieblot C, Peveri P, Vigne R, Suzan M (1995) The vif gene is essential for efficient replication of caprine arthritis encephalitis virus in goat synovial membrane cells and affects the late steps of the virus replication cycle. J Virol 69:3247–3257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Seroude V, Audoly G, Gluschankof P, Suzan M (2001) Tryptophan 95, an amino acid residue of the Caprine arthritis encephalitis virus vif protein which is essential for virus replication. Virology 280:232–242

    Article  CAS  PubMed  Google Scholar 

  51. Sauter D, Kirchhoff F (2018) Multilayered and versatile inhibition of cellular antiviral factors by HIV and SIV accessory proteins. Cytokine Growth Factor Rev 40:3–12

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Key Research and Development Program of China (2018YFD0500500) and the National Natural Science Foundation in China (no. 30771613).

Author information

Author notes

  1. Yali Fu and Dong Lu contributed equally to this work.

Authors and Affiliations

  1. School of Life Sciences, Tianjin University, No. 92, Weijin road, Nankai District, Tianjin, 300072, China

    Yali Fu, Dong Lu, Yanxin Su, Heng Chi, Jiashun Wang & Jinhai Huang

Authors
  1. Yali Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dong Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yanxin Su
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Heng Chi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jiashun Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jinhai Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceived and designed the experiments: JH H. Performed the experiments: YL F, D L, H C, YX S, and JS W. Analyzed the data: YL F and JH H. Contributed reagents/materials /analysis tools: JH H. Wrote the paper: YL F, and JH H.

Corresponding author

Correspondence to Jinhai Huang.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Handling Editor: Tim Skern.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fu, Y., Lu, D., Su, Y. et al. The Vif protein of caprine arthritis encephalitis virus inhibits interferon production. Arch Virol 165, 1557–1567 (2020). https://doi.org/10.1007/s00705-020-04637-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00705-020-04637-z

Search

Navigation