Skip to main content
SpringerLink
Log in

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

  • Published:
Archives of Virology Aims and scope Submit manuscript

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.

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

Similar content being viewed by others

References

  • H Akashi Y Inaba (1997) ArticleTitleAntigenic diversity of Akabane virus detected by monoclonal antibodies Virus Res 47 187–196 Occurrence Handle9085550 Occurrence Handle10.1016/S0168-1702(96)01415-3 Occurrence Handle1:CAS:528:DyaK2sXit1Ght7o%3D

    Article  PubMed  CAS  Google Scholar 

  • H Akashi Y Kaku X Kong H Pang (1997) ArticleTitleAntigenic and genetic comparisons of Japanese and Australian Simbu serogroup viruses: evidence for the recovery of natural virus reassortants Virus Res 50 205–213 Occurrence Handle9282785 Occurrence Handle10.1016/S0168-1702(97)00071-3 Occurrence Handle1:CAS:528:DyaK2sXlslKnsbk%3D

    Article  PubMed  CAS  Google Scholar 

  • H Akashi Y Kaku XG Kong H Pang (1997) ArticleTitleSequence determination and phylogenetic analysis of the Akabane bunyavirus S RNA genome segment J Gen Virol 78 2847–2851 Occurrence Handle9367371 Occurrence Handle1:CAS:528:DyaK2sXntVyhsLk%3D

    PubMed  CAS  Google Scholar 

  • VH Aquino ML Moreli LT Moraes Figueiredo (2003) ArticleTitleAnalysis 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 activity Arch Virol 148 19–28 Occurrence Handle12536293 Occurrence Handle10.1007/s00705-002-0913-4 Occurrence Handle1:CAS:528:DC%2BD3sXjvFGluw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • A Bridgen F Weber JK Fazakerley RM Elliott (2001) ArticleTitleBunyamwera bunyavirus nonstructural protein NSs is a nonessential gene product that contributes to viral pathogenesis Proc Natl Acad Sci USA 98 664–669 Occurrence Handle11209062 Occurrence Handle10.1073/pnas.98.2.664 Occurrence Handle1:CAS:528:DC%2BD3MXnslKmsQ%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • MJ Endres A Valsamakis F Gonzalez-Scarano N Nathanson (1990) ArticleTitleNeuroattenuated bunyavirus variant: derivation, characterization, and revertant clones J Virol 64 1927–1933 Occurrence Handle2182907 Occurrence Handle1:STN:280:By%2BB3MbhvVw%3D

    PubMed  CAS  Google Scholar 

  • MJ Endres C Griot F Gonzalez-Scarano N Nathanson (1991) ArticleTitleNeuroattenuation of an avirulent bunyavirus variant maps to the L RNA segment J Virol 65 5465–5470 Occurrence Handle1895395 Occurrence Handle1:CAS:528:DyaK3MXmtVejtbw%3D

    PubMed  CAS  Google Scholar 

  • CE Garry RF Garry (2004) ArticleTitleProteomics computational analyses suggest that the carboxyl terminal glycoproteins of Bunyaviruses are class II viral fusion protein (beta-penetrenes) Theor Biol Med Model 1 10 Occurrence Handle15544707 Occurrence Handle10.1186/1742-4682-1-10 Occurrence Handle1:CAS:528:DC%2BD2MXjs1entLk%3D

    Article  PubMed  CAS  Google Scholar 

  • C Griot A Pekosz D Lukac SS Scherer K Stillmock D Schmeidler MJ Endres F Gonzalez-Scarano N Nathanson (1993) ArticleTitlePolygenic control of neuroinvasiveness in California serogroup bunyaviruses J Virol 67 3861–3867 Occurrence Handle8510208 Occurrence Handle1:CAS:528:DyaK3sXmt1ejtb8%3D

    PubMed  CAS  Google Scholar 

  • M Hatta P Gao P Halfmann Y Kawaoka (2001) ArticleTitleMolecular basis for high virulence of Hong Kong H5N1 influenza A viruses Science 293 1840–1842 Occurrence Handle11546875 Occurrence Handle10.1126/science.1062882 Occurrence Handle1:CAS:528:DC%2BD3MXmvVSktrw%3D

    Article  PubMed  CAS  Google Scholar 

  • Y Inaba M Matumoto (1990) Akabane virus Z Dinter B Morein (Eds) Virus infections of ruminants Elsevier Science Amsterdam 467–480

    Google Scholar 

  • CU Iroegbu CR Pringle (1981) ArticleTitleGenetic interactions among viruses of the Bunyamwera complex J Virol 37 383–394 Occurrence Handle7218427 Occurrence Handle1:CAS:528:DyaL3MXotVWjtA%3D%3D

    PubMed  CAS  Google Scholar 

  • RS Janssen N Nathanson MJ Endres F Gonzalez-Scarano (1986) ArticleTitleVirulence of La Crosse virus is under polygenic control J Virol 59 1–7 Occurrence Handle3712554 Occurrence Handle1:CAS:528:DyaL28XksFGnsbk%3D

    PubMed  CAS  Google Scholar 

  • H Kurogi Y Inaba E Takahashi K Sato T Omori Y Miura Y Goto Y Fujiwara Y Hatano K Kodama S Fukuyama N Sasaki M Matumoto (1976) ArticleTitleEpizootic congenital arthrogryposis-hydranencephaly syndrome in cattle: isolation of Akabane virus from affected fetuses Arch Virol 51 67–74 Occurrence Handle962588 Occurrence Handle10.1007/BF01317835 Occurrence Handle1:STN:280:CSmB2sjhsFA%3D

    Article  PubMed  CAS  Google Scholar 

  • H Kurogi Y Inaba E Takahashi K Sato H Akashi K Satoda T Omori (1979) ArticleTitleAn attenuated strain of Akabane virus: a candidate for live virus vaccine Natl Inst Anim Health Q (Tokyo) 19 12–22 Occurrence Handle1:STN:280:Bi%2BC2czivVM%3D

    CAS  Google Scholar 

  • AC Lowen C Noonan A McLees RM Elliott (2004) ArticleTitleEfficient bunyavirus rescue from cloned cDNA Virology 330 493–500 Occurrence Handle15567443 Occurrence Handle10.1016/j.virol.2004.10.009 Occurrence Handle1:CAS:528:DC%2BD2cXhtVaks7fN

    Article  PubMed  CAS  Google Scholar 

  • GV Ludwig BA Israel BM Christensen TM Yuill KT Schultz (1991) ArticleTitleRole of La Crosse virus glycoproteins in attachment of virus to host cells Virology 181 564–571 Occurrence Handle1673039 Occurrence Handle10.1016/0042-6822(91)90889-J Occurrence Handle1:CAS:528:DyaK3MXhvVWku74%3D

    Article  PubMed  CAS  Google Scholar 

  • R Muller O Poch M Delarue DH Bishop M Bouloy (1994) ArticleTitleRift Valley fever virus L segment: correction of the sequence and possible functional role of newly identified regions conserved in RNA-dependent polymerases J Gen Virol 75 1345–1352 Occurrence Handle7515937 Occurrence Handle10.1099/0022-1317-75-6-1345

    Article  PubMed  Google Scholar 

  • Y Ogawa K Kato Y Tohya H Akashi (2007) ArticleTitleSequence determination and functional analysis of the Akabane virus (family Bunyaviridae) L RNA segment Arch Virol 152 971–979 Occurrence Handle17216138 Occurrence Handle10.1007/s00705-006-0912-y Occurrence Handle1:CAS:528:DC%2BD2sXksF2ksLY%3D

    Article  PubMed  CAS  Google Scholar 

  • A Oya T Okuno T Ogata I Kobayashi T Matsuyama (1961) ArticleTitleAkabane, a new arbor virus isolated in Japan Jpn J Med Sci Biol 14 101–108 Occurrence Handle14482934 Occurrence Handle1:STN:280:CC2D1cvksFw%3D

    PubMed  CAS  Google Scholar 

  • O Poch I Sauvaget M Delarue N Tordo (1989) ArticleTitleIdentification of four conserved motifs among the RNA-dependent polymerase encoding elements EMBO J 8 3867–3874 Occurrence Handle2555175 Occurrence Handle1:CAS:528:DyaK3cXhvVajug%3D%3D

    PubMed  CAS  Google Scholar 

  • E Pollitt J Zhao P Muscat RM Elliott (2006) ArticleTitleCharacterization of Maguari orthobunyavirus mutants suggests the nonstructural protein NSm is not essential for growth in tissue culture Virology 348 224–232 Occurrence Handle16445958 Occurrence Handle10.1016/j.virol.2005.12.026 Occurrence Handle1:CAS:528:DC%2BD28XjvVajtbc%3D

    Article  PubMed  CAS  Google Scholar 

  • CR Pringle JF Lees W Clark RM Elliott (1984) ArticleTitleGenome subunit reassortment among Bunyaviruses analysed by dot hybridization using molecularly cloned complementary DNA probes Virology 135 244–256 Occurrence Handle6547258 Occurrence Handle10.1016/0042-6822(84)90134-X Occurrence Handle1:CAS:528:DyaL2cXks1Kqs7g%3D

    Article  PubMed  CAS  Google Scholar 

  • DD Richman BR Murphy (1979) ArticleTitleThe association of the temperature-sensitive phenotype with viral attenuation in animals and humans: implications for the development and use of live virus vaccines Rev Infect Dis 1 413–433 Occurrence Handle399362 Occurrence Handle1:STN:280:Bi6D3MrgvVU%3D

    PubMed  CAS  Google Scholar 

  • X Shi A Kohl VH Leonard P Li A McLees RM Elliott (2006) ArticleTitleRequirement of the N-terminal region of orthobunyavirus nonstructural protein NSm for virus assembly and morphogenesis J Virol 80 8089–8099 Occurrence Handle16873265 Occurrence Handle10.1128/JVI.00579-06 Occurrence Handle1:CAS:528:DC%2BD28Xot1yrt7c%3D

    Article  PubMed  CAS  Google Scholar 

  • K Shinya S Hamm M Hatta H Ito T Ito Y Kawaoka (2004) ArticleTitlePB2 amino acid at position 627 affects replicative efficiency, but not cell tropism, of Hong Kong H5N1 influenza A viruses in mice Virology 320 258–266 Occurrence Handle15016548 Occurrence Handle10.1016/j.virol.2003.11.030 Occurrence Handle1:CAS:528:DC%2BD2cXhvVOqsbg%3D

    Article  PubMed  CAS  Google Scholar 

  • F Weber A Bridgen JK Fazakerley H Streitenfeld N Kessler RE Randall RM Elliott (2002) ArticleTitleBunyamwera bunyavirus nonstructural protein NSs counteracts the induction of alpha/beta interferon J Virol 76 7949–7955 Occurrence Handle12133999 Occurrence Handle10.1128/JVI.76.16.7949-7955.2002 Occurrence Handle1:CAS:528:DC%2BD38XlslOlu7c%3D

    Article  PubMed  CAS  Google Scholar 

  • S Won T Ikegami CJ Peters S Makino (2006) ArticleTitleNSm and 78-kilodalton proteins of Rift Valley fever virus are nonessential for viral replication in cell culture J Virol 80 8274–8278 Occurrence Handle16873285 Occurrence Handle10.1128/JVI.00476-06 Occurrence Handle1:CAS:528:DC%2BD28Xot1yrtbc%3D

    Article  PubMed  CAS  Google Scholar 

  • T Yanase K Yoshida S Ohashi T Kato T Tsuda (2003) ArticleTitleSequence analysis of the medium RNA segment of three Simbu serogroup viruses, Akabane, Aino, and Peaton viruses Virus Res 93 63–69 Occurrence Handle12727343 Occurrence Handle10.1016/S0168-1702(03)00066-2 Occurrence Handle1:CAS:528:DC%2BD3sXjtlSltL0%3D

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Veterinary Microbiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan

    Y. Ogawa, K. Kato, Y. Tohya & H. Akashi

Authors
  1. Y. Ogawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K. Kato
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Y. Tohya
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H. Akashi
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ogawa, Y., Kato, K., Tohya, Y. et al. Characterization of temperature-sensitive Akabane virus mutants and their roles in attenuation. Arch Virol 152, 1679–1686 (2007). https://doi.org/10.1007/s00705-007-0991-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00705-007-0991-4

Keywords

Search

Navigation