Reverse Genetics of Bunyaviruses

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The family Bunyaviridae contains several serious human pathogens, causing encephalitis, febrile illnesses or hemorrhagic fevers. Important members are La Crosse virus, Oropouche virus, Rift Valley fever virus, Crimean-Congo hemorrhagic fever virus and the Hantaviruses. All bunyaviruses are enveloped and have a tri-segmented single-stranded RNA genome of negative or ambisense polarity, replicate in the cytoplasm, and bud into the Golgi apparatus. They encode four common structural proteins: the viral polymerase (L) on the large (L) segment, two glycoproteins (Gn and Gc) on the medium (M) segment, and the viral nucleocapsid protein (N) on the smallest (S) segment. Viruses within some genera also encode non-structural proteins, either on the M segment (termed NSm) or on the S segment (NSs). For the targeted mutagenesis of viruses, the rescue of infectious viruses entirely from cloned cDNA plasmids ("reverse genetics") is mandatory. The so-called minireplicon systems represent the first step towards bunyavirus reverse genetics. Minireplicon systems are used to reconstitute recombinant viral nucleocapsids containing an artificial, genome-like reporter RNA (minireplicon). If the minireplicon is replaced by full-length cDNA constructs of the viral gene segments, infectious viruses can be recovered.Using these methods, we study the replication, host cell interactions, and virulence mechanisms of bunyaviruses.

Additional information: http://www.ukl.uniklinik-freiburg.de/microbio
contact person: PD Dr. Friedemann Weber
Phone: (0761) 2036614
Email: friedemann.weber@uniklinik-freiburg.de

Start of project: 01.12.2000
End of project: (unlimited)

Albert-Ludwigs-University Freiburg
Weber, Friedemann
Department für Medizinische Mikrobiologie und Hygiene
Institut für Virologie
Hermann-Herder-Strasse 11
79104 Freiburg
Germany

Phone: +49 761 203 6534
Fax: +49 761 203 6626
http://www.virologie.uniklinik-freiburg.de
Actual Research Report

• DFG
• IAEA

• Blakqori G, Weber F: Efficient cDNA-based rescue of La Crosse Bunyaviruses expressing or lacking the nonstructural protein NSs. J Virol, 2005; 79: 10420-10428.
• Blakqori G, Kochs G, Haller O, Weber F: Functional L polymerase of La Crosse virus allows in vivo reconstitution of recombinant nucleocapsids J Gen Virol, 2003; 84: 1207-1214.
• Bridgen A., Weber F., Fazakerley J.K., Elliott R.M.: Bunyamwera bunyavirus nonstructural protein NSs is a nonessential gene product that contributes to viral pathogenesis. P Natl Acad Sci Usa, 2001; 98 (2): 664-669.
• Weber F., Dunn E.F., Bridgen A., Elliott R.M.: The Bunyamwera virus nonstructural protein NSs is a repressor of the viral polymerase. Virology, 2001; 281: 67-74.