2016年
The high degree of sequence plasticity of the arenavirus noncoding intergenic region (IGR) enables the use of a nonviral universal synthetic IGR to attenuate arenaviruses
Journal of Virology
- ,
- ,
- ,
- 巻
- 90
- 号
- 6
- 開始ページ
- 3187
- 終了ページ
- 3197
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1128/JVI.03145-15
- 出版者・発行元
- AMER SOC MICROBIOLOGY
Hemorrhagic fever arenaviruses (HFAs) pose important public health problems in regions where they are endemic. Concerns about human-pathogenic arenaviruses are exacerbated because of the lack of FDA-licensed arenavirus vaccines and because current antiarenaviral therapy is limited to an off-label use of ribavirin that is only partially effective. We have recently shown that the noncoding intergenic region (IGR) present in each arenavirus genome segment, the S and L segments (S-IGR and L-IGR, respectively), plays important roles in the control of virus protein expression and that this knowledge could be harnessed for the development of live-attenuated vaccine strains to combat HFAs. In this study, we further investigated the sequence plasticity of the arenavirus IGR. We demonstrate that recombinants of the prototypic arenavirus lymphocytic choriomeningitis virus (rLCMVs), whose S-IGRs were replaced by the S-IGR of Lassa virus (LASV) or an entirely nonviral S-IGR-like sequence (Ssyn), are viable, indicating that the function of S-IGR tolerates a high degree of sequence plasticity. In addition, rLCMVs whose L-IGRs were replaced by Ssyn or S-IGRs of the very distantly related reptarenavirus Golden Gate virus (GGV) were viable and severely attenuated in vivo but able to elicit protective immunity against a lethal challenge with wild-type LCMV. Our findings indicate that replacement of L-IGR by a nonviral Ssyn could serve as a universal molecular determinant of arenavirus attenuation.
- リンク情報
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- DOI
- https://doi.org/10.1128/JVI.03145-15
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/26739049
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000374110600041&DestApp=WOS_CPL
- Scopus
- https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84961124642&origin=inward 本文へのリンクあり
- Scopus Citedby
- https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=84961124642&origin=inward
- ID情報
-
- DOI : 10.1128/JVI.03145-15
- ISSN : 0022-538X
- eISSN : 1098-5514
- PubMed ID : 26739049
- SCOPUS ID : 84961124642
- Web of Science ID : WOS:000374110600041