Advertisement

Archives of Virology

, Volume 152, Issue 9, pp 1679–1686 | Cite as

Characterization of temperature-sensitive Akabane virus mutants and their roles in attenuation

  • Y. Ogawa
  • K. Kato
  • Y. Tohya
  • H. Akashi
Article

Summary

Akabane virus (AKAV) of the genus Orthobunyavirus in the family Bunyaviridae is an important animal pathogen; however, studies on AKAV biology are scarce. Therefore, we generated temperature-sensitive (ts) mutants of AKAV in order to study its pathogenesis. The ts AKAV mutants were generated by incubating the virulent OBE-1 strain with the chemical mutagen 5-fluorouracil. Each ts mutant was inoculated intracerebrally into mice to assess its virulence, and the genomic sequences of the attenuated mutants were also determined. Three of the twelve ts mutants studied showed a mortality rate of less than 10%. Although no mutation was detected in the S RNA segment of these three mutants, amino acid substitutions were observed in both the M and L RNA segments. Three of the mutants and the wild-type virus demonstrated a similar pattern of immunoreactivity in an ELISA with anti-Gc monoclonal antibodies. On the other hand, using a minireplicon system, the level of L protein activity of each ts mutant decreased as the temperature increased. These results suggest that the L RNA segment could be involved in the virulence of AKAV, which increases our understanding of how the viral gene products contribute to pathogenesis.

Keywords

Rift Valley Fever Virus Viral Gene Product Viral Fusion Protein Akabane Virus Simbu Serogroup Virus 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Akashi, H, Inaba, Y 1997Antigenic diversity of Akabane virus detected by monoclonal antibodiesVirus Res47187196PubMedCrossRefGoogle Scholar
  2. Akashi, H, Kaku, Y, Kong, X, Pang, H 1997Antigenic and genetic comparisons of Japanese and Australian Simbu serogroup viruses: evidence for the recovery of natural virus reassortantsVirus Res50205213PubMedCrossRefGoogle Scholar
  3. Akashi, H, Kaku, Y, Kong, XG, Pang, H 1997Sequence determination and phylogenetic analysis of the Akabane bunyavirus S RNA genome segmentJ Gen Virol7828472851PubMedGoogle Scholar
  4. Aquino, VH, Moreli, ML, Moraes Figueiredo, LT 2003Analysis of Oropouche virus L protein amino acid sequence showed the presence of an additional conserved region that could harbour an important role for the polymerase activityArch Virol1481928PubMedCrossRefGoogle Scholar
  5. Bridgen, A, Weber, F, Fazakerley, JK, Elliott, RM 2001Bunyamwera bunyavirus nonstructural protein NSs is a nonessential gene product that contributes to viral pathogenesisProc Natl Acad Sci USA98664669PubMedCrossRefGoogle Scholar
  6. Endres, MJ, Valsamakis, A, Gonzalez-Scarano, F, Nathanson, N 1990Neuroattenuated bunyavirus variant: derivation, characterization, and revertant clonesJ Virol6419271933PubMedGoogle Scholar
  7. Endres, MJ, Griot, C, Gonzalez-Scarano, F, Nathanson, N 1991Neuroattenuation of an avirulent bunyavirus variant maps to the L RNA segmentJ Virol6554655470PubMedGoogle Scholar
  8. Garry, CE, Garry, RF 2004Proteomics computational analyses suggest that the carboxyl terminal glycoproteins of Bunyaviruses are class II viral fusion protein (beta-penetrenes)Theor Biol Med Model110PubMedCrossRefGoogle Scholar
  9. Griot, C, Pekosz, A, Lukac, D, Scherer, SS, Stillmock, K, Schmeidler, D, Endres, MJ, Gonzalez-Scarano, F, Nathanson, N 1993Polygenic control of neuroinvasiveness in California serogroup bunyavirusesJ Virol6738613867PubMedGoogle Scholar
  10. Hatta, M, Gao, P, Halfmann, P, Kawaoka, Y 2001Molecular basis for high virulence of Hong Kong H5N1 influenza A virusesScience29318401842PubMedCrossRefGoogle Scholar
  11. Inaba, Y, Matumoto, M 1990Akabane virusDinter, ZMorein, B eds. Virus infections of ruminantsElsevier ScienceAmsterdam467480Google Scholar
  12. Iroegbu, CU, Pringle, CR 1981Genetic interactions among viruses of the Bunyamwera complexJ Virol37383394PubMedGoogle Scholar
  13. Janssen, RS, Nathanson, N, Endres, MJ, Gonzalez-Scarano, F 1986Virulence of La Crosse virus is under polygenic controlJ Virol5917PubMedGoogle Scholar
  14. Kurogi, H, Inaba, Y, Takahashi, E, Sato, K, Omori, T, Miura, Y, Goto, Y, Fujiwara, Y, Hatano, Y, Kodama, K, Fukuyama, S, Sasaki, N, Matumoto, M 1976Epizootic congenital arthrogryposis-hydranencephaly syndrome in cattle: isolation of Akabane virus from affected fetusesArch Virol516774PubMedCrossRefGoogle Scholar
  15. Kurogi, H, Inaba, Y, Takahashi, E, Sato, K, Akashi, H, Satoda, K, Omori, T 1979An attenuated strain of Akabane virus: a candidate for live virus vaccineNatl Inst Anim Health Q (Tokyo)191222Google Scholar
  16. Lowen, AC, Noonan, C, McLees, A, Elliott, RM 2004Efficient bunyavirus rescue from cloned cDNAVirology330493500PubMedCrossRefGoogle Scholar
  17. Ludwig, GV, Israel, BA, Christensen, BM, Yuill, TM, Schultz, KT 1991Role of La Crosse virus glycoproteins in attachment of virus to host cellsVirology181564571PubMedCrossRefGoogle Scholar
  18. Muller, R, Poch, O, Delarue, M, Bishop, DH, Bouloy, M 1994Rift Valley fever virus L segment: correction of the sequence and possible functional role of newly identified regions conserved in RNA-dependent polymerasesJ Gen Virol7513451352PubMedCrossRefGoogle Scholar
  19. Ogawa, Y, Kato, K, Tohya, Y, Akashi, H 2007Sequence determination and functional analysis of the Akabane virus (family Bunyaviridae) L RNA segmentArch Virol152971979PubMedCrossRefGoogle Scholar
  20. Oya, A, Okuno, T, Ogata, T, Kobayashi, I, Matsuyama, T 1961Akabane, a new arbor virus isolated in JapanJpn J Med Sci Biol14101108PubMedGoogle Scholar
  21. Poch, O, Sauvaget, I, Delarue, M, Tordo, N 1989Identification of four conserved motifs among the RNA-dependent polymerase encoding elementsEMBO J838673874PubMedGoogle Scholar
  22. Pollitt, E, Zhao, J, Muscat, P, Elliott, RM 2006Characterization of Maguari orthobunyavirus mutants suggests the nonstructural protein NSm is not essential for growth in tissue cultureVirology348224232PubMedCrossRefGoogle Scholar
  23. Pringle, CR, Lees, JF, Clark, W, Elliott, RM 1984Genome subunit reassortment among Bunyaviruses analysed by dot hybridization using molecularly cloned complementary DNA probesVirology135244256PubMedCrossRefGoogle Scholar
  24. Richman, DD, Murphy, BR 1979The association of the temperature-sensitive phenotype with viral attenuation in animals and humans: implications for the development and use of live virus vaccinesRev Infect Dis1413433PubMedGoogle Scholar
  25. Shi, X, Kohl, A, Leonard, VH, Li, P, McLees, A, Elliott, RM 2006Requirement of the N-terminal region of orthobunyavirus nonstructural protein NSm for virus assembly and morphogenesisJ Virol8080898099PubMedCrossRefGoogle Scholar
  26. Shinya, K, Hamm, S, Hatta, M, Ito, H, Ito, T, Kawaoka, Y 2004PB2 amino acid at position 627 affects replicative efficiency, but not cell tropism, of Hong Kong H5N1 influenza A viruses in miceVirology320258266PubMedCrossRefGoogle Scholar
  27. Weber, F, Bridgen, A, Fazakerley, JK, Streitenfeld, H, Kessler, N, Randall, RE, Elliott, RM 2002Bunyamwera bunyavirus nonstructural protein NSs counteracts the induction of alpha/beta interferonJ Virol7679497955PubMedCrossRefGoogle Scholar
  28. Won, S, Ikegami, T, Peters, CJ, Makino, S 2006NSm and 78-kilodalton proteins of Rift Valley fever virus are nonessential for viral replication in cell cultureJ Virol8082748278PubMedCrossRefGoogle Scholar
  29. Yanase, T, Yoshida, K, Ohashi, S, Kato, T, Tsuda, T 2003Sequence analysis of the medium RNA segment of three Simbu serogroup viruses, Akabane, Aino, and Peaton virusesVirus Res936369PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Y. Ogawa
    • 1
  • K. Kato
    • 1
  • Y. Tohya
    • 1
  • H. Akashi
    • 1
  1. 1.Department of Veterinary Microbiology, Graduate School of Agricultural and Life SciencesThe University of TokyoTokyoJapan

Personalised recommendations