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Generation of mutant Uukuniemi viruses lacking the nonstructural protein NSs by reverse genetics indicates that NSs is a weak interferon antagonist.
Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
2015 (English)In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 89, no 9, 4849-4856 p.Article in journal (Refereed) Published
Abstract [en]

Uukuniemi virus (UUKV) is a tick-borne member of the Phlebovirus genus (family Bunyaviridae) and has been widely used as a safe laboratory model to study aspects of bunyavirus replication. Recently, a number of new tick-borne phleboviruses have been discovered, some of which, like severe fever with thrombocytopenia syndrome virus and Heartland virus, are highly pathogenic in man. UUKV could now serve as a useful comparator to understand the molecular basis for the different pathogenicities of these related viruses. We established a reverse genetics system to recover UUKV entirely from cDNA clones. We generated two recombinant viruses, one in which the nonstructural protein NSs open reading frame was deleted from the S segment and one in which the NSs gene was replaced with GFP, allowing convenient visualization of viral infection. We show that the UUKV NSs protein acts as a weak interferon antagonist in human cells, but it is unable to completely counteract the interferon response, which could serve as an explanation for its inability to cause disease in man.

IMPORTANCE: Uukuniemi virus (UUKV) is a tick-borne phlebovirus that is apathogenic for man and has been used as a convenient model to investigate aspects of phlebovirus replication. Recently new tick-borne phleboviruses have emerged, such as severe fever with thrombocytopenia syndrome virus in China and Heartland virus in the US, that are highly pathogenic, and UUKV will now serve as a comparison to aid understanding of the molecular basis for the virulence of these new viruses. To help such investigations, we have developed a reverse genetics system for UUKV that permits manipulation of the viral genome. We generated viruses lacking the nonstructural protein NSs and show that UUKV NSs is a weak interferon antagonist. In addition, we created a virus that expresses GFP and thus allows convenient monitoring of virus replication. These new tools represent a significant advance in the study of tick-borne phleboviruses.

Place, publisher, year, edition, pages
2015. Vol. 89, no 9, 4849-4856 p.
National Category
Microbiology
Identifiers
URN: urn:nbn:se:umu:diva-100395DOI: 10.1128/JVI.03511-14ISI: 000352219600014PubMedID: 25673721OAI: oai:DiVA.org:umu-100395DiVA: diva2:792060
Available from: 2015-03-03 Created: 2015-03-03 Last updated: 2017-12-04Bibliographically approved

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