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dc.contributor.authorTilston-Lunel, Natasha L.
dc.contributor.authorAcrani, Gustavo Olszanski
dc.contributor.authorRandall, Richard E.
dc.contributor.authorElliott, Richard M.
dc.identifier.citationTilston-Lunel , N L , Acrani , G O , Randall , R E & Elliott , R M 2016 , ' Generation of recombinant Oropouche viruses lacking the nonstructural protein NSm or NSs ' , Journal of Virology , vol. 90 , no. 5 , pp. 2616-2627 .
dc.identifier.otherPURE: 243431410
dc.identifier.otherPURE UUID: be1a350f-7087-48c0-886e-d35f9428316d
dc.identifier.otherRIS: urn:C69F723BE0138C52C94893845954BC98
dc.identifier.otherScopus: 84961167427
dc.identifier.otherORCID: /0000-0002-9304-6678/work/60427025
dc.identifier.otherWOS: 000370005400038
dc.descriptionWellcome Trust provided funding to Richard M. Elliott under grant number 99220. Medical Research Council (MRC) provided funding to Natasha Louise Tilston-Lunel under grant number 1101085. FAPESP-São Paulo Research Foundation provided funding to Gustavo Olszanski Acrani under grant number 2013/02798-0.en
dc.description.abstractOropouche virus (OROV) is a midge-borne human pathogen with a geographic distribution in South America. OROV was first isolated in 1955, and since then, it has been known to cause recurring outbreaks of a dengue-like illness in the Amazonian regions of Brazil. OROV, however, remains one of the most poorly understood emerging viral zoonoses. Here we describe the successful recovery of infectious OROV entirely from cDNA copies of its genome and generation of OROV mutant viruses lacking either the NSm or the NSs coding region. Characterization of the recombinant viruses carried out in vitro demonstrated that the NSs protein of OROV is an interferon (IFN) antagonist as in other NSs-encoding bunyaviruses. Additionally, we demonstrate the importance of the nine C-terminal amino acids of OROV NSs in IFN antagonistic activity. OROV was also found to be sensitive to IFN-α when cells were pretreated; however, the virus was still capable of replicating at doses as high as 10,000 U/ml of IFN-α, in contrast to the family prototype BUNV. We found that OROV lacking the NSm protein displayed characteristics similar to those of the wild-type virus, suggesting that the NSm protein is dispensable for virus replication in the mammalian and mosquito cell lines that were tested. IMPORTANCE Oropouche virus (OROV) is a public health threat in Central and South America, where it causes periodic outbreaks of dengue-like illness. In Brazil, OROV is the second most frequent cause of arboviral febrile illness after dengue virus, and with the current rates of urban expansion, more cases of this emerging viral zoonosis could occur. To better understand the molecular biology of OROV, we have successfully rescued the virus along with mutants. We have established that the C terminus of the NSs protein is important in interferon antagonism and that the NSm protein is dispensable for virus replication in cell culture. The tools described in this paper are important in terms of understanding this important yet neglected human pathogen.
dc.relation.ispartofJournal of Virologyen
dc.rightsCopyright © 2016, American Society for Microbiology. This work is made available online in accordance with the publisher’s policies. This is the author created, accepted version manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at
dc.subjectQH301 Biologyen
dc.subjectSDG 3 - Good Health and Well-beingen
dc.titleGeneration of recombinant Oropouche viruses lacking the nonstructural protein NSm or NSsen
dc.typeJournal articleen
dc.contributor.sponsorThe Wellcome Trusten
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.contributor.institutionUniversity of St Andrews. School of Biologyen
dc.description.statusPeer revieweden

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