Skip to main content

Advertisement

Log in

Genome comparison of virulent and avirulent strains of the Pichinde arenavirus

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

Abstract

A virulent (P18) strain of the Pichinde arenavirus produces a disease in guinea pigs that somewhat mimics human Lassa fever, whereas an avirulent (P2) strain of this virus is attenuated in infected animals. It has been speculated that the composition of viral genomes may confer the degree of virulence in an infected host; the complete sequence of the viral genomes, however, is not known. Here, we provide for the first time genomic sequences of the S and L segments for both the P2 and P18 strains. Sequence comparisons identify three mutations in the GP1 subunit of the viral glycoprotein, one in the nucleoprotein NP, and five in the viral RNA polymerase L protein. These mutations, alone or in combination, may contribute to the acquired virulence of Pichinde virus infection in animals. The three amino acid changes in the variable region of the GP1 glycoprotein subunit may affect viral entry by altering its receptor-binding activity. While NP has previously been shown to modulate host immune responses to viral infection, we found that the R374 K change in this protein does not affect the NP function of suppressing interferon-β expression. Four out of the five amino acid changes in the L protein occur in a small region of the protein that may contribute to viral virulence by enhancing its function in viral genomic RNA synthesis.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Aronson JF, Herzog NK, Jerrells TR (1994) Pathological and virological features of arenavirus disease in guinea pigs. Comparison of two Pichinde virus strains. Am J Pathol 145:228–235

    PubMed  CAS  Google Scholar 

  2. Aronson JF, Herzog NK, Jerrells TR (1995) Tumor necrosis factor and the pathogenesis of Pichinde virus infection in guinea pigs. Am J Trop Med Hyg 52:262–269

    PubMed  CAS  Google Scholar 

  3. Baize S, Kaplon J, Faure C, Pannetier D, Georges-Courbot MC, Deubel V (2004) Lassa virus infection of human dendritic cells and macrophages is productive but fails to activate cells. J Immunol 172:2861–2869

    PubMed  CAS  Google Scholar 

  4. Beyer WR, Popplau D, Garten W, von Laer D, Lenz O (2003) Endoproteolytic processing of the lymphocytic choriomeningitis virus glycoprotein by the subtilase SKI-1/S1P. J Virol 77:2866–2872

    Article  PubMed  CAS  Google Scholar 

  5. Bowick GC, Fennewald SM, Elsom BL, Aronson JF, Luxon BA, Gorenstein DG, Herzog NK (2006) Differential signaling networks induced by mild and lethal hemorrhagic fever virus infections. J Virol 80:10248–10252

    Article  PubMed  CAS  Google Scholar 

  6. Bowick GC, Fennewald SM, Scott EP, Zhang L, Elsom BL, Aronson JF, Spratt HM, Luxon BA, Gorenstein DG, Herzog NK (2007) Identification of differentially activated cell-signaling networks associated with pichinde virus pathogenesis by using systems kinomics. J Virol 81:1923–1933

    Article  PubMed  CAS  Google Scholar 

  7. Buchmeier MJ, Bowen MD, Peters CJ (2001) Arenaviridae: the viruses and their replication. In: Knipe DM, Howley PM (eds) Fields virology, vol 2. Lippincott-Raven, Philadelphia, pp 1635–1668

    Google Scholar 

  8. Connolly BM, Jenson AB, Peters CJ, Geyer SJ, Barth JF, McPherson RA (1993) Pathogenesis of Pichinde virus infection in strain 13 guinea pigs: an immunocytochemical, virologic, and clinical chemistry study. Am J Trop Med Hyg 49:10–24

    PubMed  CAS  Google Scholar 

  9. Cornu TI, de la Torre JC (2001) RING finger Z protein of lymphocytic choriomeningitis virus (LCMV) inhibits transcription and RNA replication of an LCMV S-segment minigenome. J Virol 75:9415–9426

    Article  PubMed  CAS  Google Scholar 

  10. Cornu TI, de la Torre JC (2002) Characterization of the arenavirus RING finger Z protein regions required for Z-mediated inhibition of viral RNA synthesis. J Virol 76:6678–6688

    Article  PubMed  CAS  Google Scholar 

  11. Eichler R, Strecker T, Kolesnikova L, ter Meulen J, Weissenhorn W, Becker S, Klenk HD, Garten W, Lenz O (2004) Characterization of the Lassa virus matrix protein Z: electron microscopic study of virus-like particles and interaction with the nucleoprotein (NP). Virus Res 100:249–255

    Article  PubMed  CAS  Google Scholar 

  12. Feldmann H, Volchkov VE, Volchkova VA, Klenk HD (1999) The glycoproteins of Marburg and Ebola virus and their potential roles in pathogenesis. Arch Virol Suppl 15:159–169

    PubMed  CAS  Google Scholar 

  13. Feldmann H, Volchkov VE, Volchkova VA, Stroher U, Klenk HD (2001) Biosynthesis and role of filoviral glycoproteins. J Gen Virol 82:2839–2848

    PubMed  CAS  Google Scholar 

  14. Fennewald SM, Aronson JF, Zhang L, Herzog NK (2002) Alterations in NF-kappaB and RBP-Jkappa by arenavirus infection of macrophages in vitro and in vivo. J Virol 76:1154–1162

    PubMed  CAS  Google Scholar 

  15. Franze-Fernandez MT, Iapalucci S, Lopez N, Rossi C (1993) Subgenomic RNAs of Tacaribe virus. In: Salvato MS (ed) The arenaviridae. Plenum Press, New York, pp 113–132

    Google Scholar 

  16. Freed EO (2003) The HIV-TSG101 interface: recent advances in a budding field. Trends Microbiol 11:56–59

    Article  PubMed  CAS  Google Scholar 

  17. Garcia-Sastre A (2001) Inhibition of interferon-mediated antiviral responses by influenza A viruses and other negative-strand RNA viruses. Virology 279:375–384

    Article  PubMed  CAS  Google Scholar 

  18. Garcin D, Rochat S, Kolakofsky D (1993) The Tacaribe arenavirus small zinc finger protein is required for both mRNA synthesis and genome replication. J Virol 67:807–812

    PubMed  CAS  Google Scholar 

  19. Glaser L, Stevens J, Zamarin D, Wilson IA, Garcia-Sastre A, Tumpey TM, Basler CF, Taubenberger JK, Palese P (2005) A single amino acid substitution in 1918 influenza virus hemagglutinin changes receptor binding specificity. J Virol 79:11533–11536

    Article  PubMed  CAS  Google Scholar 

  20. Gunther S, Lenz O (2004) Lassa virus. Crit Rev Clin Lab Sci 41:339–390

    Article  PubMed  CAS  Google Scholar 

  21. Hass M, Westerkofsky M, Muller S, Becker-Ziaja B, Busch C, Gunther S (2006) Mutational analysis of the lassa virus promoter. J Virol 80:12414–12419

    Article  PubMed  CAS  Google Scholar 

  22. Hatta M, Gao P, Halfmann P, Kawaoka Y (2001) Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses. Science 293:1840–1842

    Article  PubMed  CAS  Google Scholar 

  23. Iapalucci S, Lopez N, Franze-Fernandez MT (1991) The 3′ end termini of the Tacaribe arenavirus subgenomic RNAs. Virology 182:269–278

    Article  PubMed  CAS  Google Scholar 

  24. Jacamo R, Lopez N, Wilda M, Franze-Fernandez MT (2003) Tacaribe virus Z protein interacts with the L polymerase protein to inhibit viral RNA synthesis. J Virol 77:10383–10393

    Article  PubMed  CAS  Google Scholar 

  25. Jahrling PB, Hesse RA, Rhoderick JB, Elwell MA, Moe JB (1981) Pathogenesis of a pichinde virus strain adapted to produce lethal infections in guinea pigs. Infect Immun 32:872–880

    PubMed  CAS  Google Scholar 

  26. Johnson KM, McCormick JB, Webb PA, Smith ES, Elliott LH, King IJ (1987) Clinical virology of Lassa fever in hospitalized patients. J Infect Dis 155:456–464

    PubMed  CAS  Google Scholar 

  27. Katz MA, Starr JF (1990) Pichinde virus infection in strain 13 guniea pigs reduces intestinal protein reflection coefficient with compensation. J Infect Dis 162:1304–1308

    PubMed  CAS  Google Scholar 

  28. Kirk WE, Cash P, Peters CJ, Bishop DH (1980) Formation and characterization of an intertypic lymphocytic choriomeningitis recombinant virus. J Gen Virol 51:213–218

    Article  PubMed  CAS  Google Scholar 

  29. Lee KJ, Perez M, Pinschewer DD, de la Torre JC (2002) Identification of the lymphocytic choriomeningitis virus (LCMV) proteins required to rescue LCMV RNA analogs into LCMV-like particles. J Virol 76:6393–6397

    Article  PubMed  CAS  Google Scholar 

  30. Lenz O, ter Meulen J, Klenk HD, Seidah NG, Garten W (2001) The Lassa virus glycoprotein precursor GP-C is proteolytically processed by subtilase SKI-1/S1P. Proc Natl Acad Sci USA 98:12701–12705

    Article  PubMed  CAS  Google Scholar 

  31. Lopez N, Jacamo R, Franze-Fernandez MT (2001) Transcription and RNA replication of tacaribe virus genome and antigenome analogs require N and L proteins: Z protein is an inhibitor of these processes. J Virol 75:12241–12251

    Article  PubMed  CAS  Google Scholar 

  32. Lopez N, Franze-Fernandez MT (2007) A single stem-loop structure in Tacaribe arenavirus intergenic region is essential for transcription termination but is not required for a correct initiation of transcription and replication. Virus Res 124:237–244

    Article  PubMed  CAS  Google Scholar 

  33. Lukashevich IS, Maryankova R, Vladyko AS, Nashkevich N, Koleda S, Djavani M, Horejsh D, Voitenok NN, Salvato MS (1999) Lassa and Mopeia virus replication in human monocytes/macrophages and in endothelial cells: different effects on IL-8 and TNF-alpha gene expression. J Med Virol 59:552–560

    Article  PubMed  CAS  Google Scholar 

  34. Mahanty S, Hutchinson K, Agarwal S, McRae M, Rollin PE, Pulendran B (2003) Cutting edge: impairment of dendritic cells and adaptive immunity by Ebola and Lassa viruses. J Immunol 170:2797–2801

    PubMed  CAS  Google Scholar 

  35. Martinez-Sobrido L, Zuniga EI, Rosario D, Garcia-Sastre A, de la Torre JC (2006) Inhibition of the type I interferon response by the nucleoprotein of the prototypic arenavirus lymphocytic choriomeningitis virus. J Virol 80:9192–9199

    Article  PubMed  CAS  Google Scholar 

  36. Martinez-Sobrido L, Giannakas P, Cubitt B, Garcia-Sastre A, de la Torre JC (2007) Differential inhibition of type I interferon induction by arenavirus nucleoproteins. J Virol 81:12696–12703

    Article  PubMed  CAS  Google Scholar 

  37. Matloubian M, Kolhekar SR, Somasundaram T, Ahmed R (1993) Molecular determinants of macrophage tropism and viral persistence: importance of single amino acid changes in the polymerase and glycoprotein of lymphocytic choriomeningitis virus. J Virol 67:7340–7349

    PubMed  CAS  Google Scholar 

  38. McCormick JB, Webb PA, Krebs JW, Johnson KM, Smith ES (1987) A prospective study of the epidemiology and ecology of Lassa fever. J Infect Dis 155:437–444

    PubMed  CAS  Google Scholar 

  39. Perez M, Craven RC, de la Torre JC (2003) The small RING finger protein Z drives arenavirus budding: implications for antiviral strategies. Proc Natl Acad Sci USA 100:12978–12983

    Article  PubMed  CAS  Google Scholar 

  40. Perez M, de la Torre JC (2003) Characterization of the genomic promoter of the prototypic arenavirus lymphocytic choriomeningitis virus. J Virol 77:1184–1194

    Article  PubMed  CAS  Google Scholar 

  41. Pinschewer DD, Perez M, de la Torre JC (2003) Role of the virus nucleoprotein in the regulation of lymphocytic choriomeningitis virus transcription and RNA replication. J Virol 77:3882–3887

    Article  PubMed  CAS  Google Scholar 

  42. Pinschewer DD, Perez M, de la Torre JC (2005) Dual role of the lymphocytic choriomeningitis virus intergenic region in transcription termination and virus propagation. J Virol 79:4519–4526

    Article  PubMed  CAS  Google Scholar 

  43. Poch O, Sauvaget I, Delarue M, Tordo N (1989) Identification of four conserved motifs among the RNA-dependent polymerase encoding elements. Embo J 8:3867–3874

    PubMed  CAS  Google Scholar 

  44. Riviere Y, Ahmed R, Southern PJ, Buchmeier MJ, Oldstone MB (1985) Genetic mapping of lymphocytic choriomeningitis virus pathogenicity: virulence in guinea pigs is associated with the L RNA segment. J Virol 55:704–709

    PubMed  CAS  Google Scholar 

  45. Rogers GN, Paulson JC, Daniels RS, Skehel JJ, Wilson IA, Wiley DC (1983) Single amino acid substitutions in influenza haemagglutinin change receptor binding specificity. Nature 304:76–78

    Article  PubMed  CAS  Google Scholar 

  46. Salvato M, Borrow P, Shimomaye E, Oldstone MB (1991) Molecular basis of viral persistence: a single amino acid change in the glycoprotein of lymphocytic choriomeningitis virus is associated with suppression of the antiviral cytotoxic T-lymphocyte response and establishment of persistence. J Virol 65:1863–1869

    PubMed  CAS  Google Scholar 

  47. Stevens J, Blixt O, Tumpey TM, Taubenberger JK, Paulson JC, Wilson IA (2006) Structure and receptor specificity of the hemagglutinin from an H5N1 influenza virus. Science 312:404–410

    Article  PubMed  CAS  Google Scholar 

  48. Strecker T, Eichler R, Meulen J, Weissenhorn W, Dieter Klenk H, Garten W, Lenz O (2003) Lassa virus Z protein is a matrix protein and sufficient for the release of virus-like particles [corrected]. J Virol 77:10700–10705

    Article  PubMed  CAS  Google Scholar 

  49. Wahl-Jensen VM, Afanasieva TA, Seebach J, Stroher U, Feldmann H, Schnittler HJ (2005) Effects of Ebola virus glycoproteins on endothelial cell activation and barrier function. J Virol 79:10442–10450

    Article  PubMed  CAS  Google Scholar 

  50. Wilson SM, Clegg JC (1991) Sequence analysis of the S RNA of the African arenavirus Mopeia: an unusual secondary structure feature in the intergenic region. Virology 180:543–552

    Article  PubMed  CAS  Google Scholar 

  51. Zhang L, Marriott K, Aronson JF (1999) Sequence analysis of the small RNA segment of guinea pig-passaged Pichinde virus variants. Am J Trop Med Hyg 61:220–225

    PubMed  CAS  Google Scholar 

  52. Zhang L, Marriott KA, Harnish DG, Aronson JF (2001) Reassortant analysis of guinea pig virulence of pichinde virus variants. Virology 290:30–38

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This research was supported by the Emory University Research Committee (URC) and the Southeast Regional Center of Excellence for Emerging Infections and Biodefense (SERCEB) to HL and YL, the Emory Digestive Diseases Research and Development Center P/F fund (DK64399) and the Center for AIDS Research (CFAR P30 AI050409) to HL, and the pilot project component of Dr. Ahmed’s U19 grant (RFA-AI-02-042) to YL.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Hinh Ly or Yuying Liang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lan, S., McLay, L., Aronson, J. et al. Genome comparison of virulent and avirulent strains of the Pichinde arenavirus . Arch Virol 153, 1241–1250 (2008). https://doi.org/10.1007/s00705-008-0101-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00705-008-0101-2

Keywords

Navigation