title: Nonstructural proteins NS2-3 and NS4A of classical swine fever virus: essential features for infectious particle formation.
abstract: The nonstructural protein NS2-3 of pestiviruses undergoes tightly regulated processing. For bovine viral diarrhea virus it was shown that uncleaved NS2-3 is required for infectious particle formation while cleaved NS3 is essential for genome replication. To further investigate the functions of NS2-3 and NS4A in the pestivirus life cycle, we established T7 RNA polymerase-dependent trans-complementation for p7-NS2-3-4A of classical swine fever virus (CSFV). Expression of NS2-3 and NS4A in trans restored the production of infectious particles from genomes lacking NS2-3 expression. Co-expression of cleaved NS4A was essential. None of the enzymatic activities harbored by NS2-3 were required for infectious particle formation. Importantly, expression of uncleavable NS2-3 together with NS4A rescued infectious particles from a genome lacking NS2, demonstrating that cleaved NS2 per se has no additional essential function. These data indicate that NS2-3 and NS3, each in association with NS4A, have independent functions in the CSFV life cycle.
authors.affiliation: Institute of Virology and Immunoprophylaxis, Sensemattstrasse 293, CH-3147 Mittelhäusern, Switzerland. herve.moulin@ivi.admin.ch
authors.forename: Hervé R
authors.initials: HR
authors.lastname: Moulin
authors.forename: Torsten
authors.initials: T
authors.lastname: Seuberlich
authors.forename: Oliver
authors.initials: O
authors.lastname: Bauhofer
authors.forename: Lea C
authors.initials: LC
authors.lastname: Bennett
authors.forename: Jon-Duri
authors.initials: JD
authors.lastname: Tratschin
authors.forename: Martin A
authors.initials: MA
authors.lastname: Hofmann
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ruggli
mesh_terms: D000818:Animals; D002460:Cell Line; D006692:Classical Swine Fever Virus / Q000235:genetics / Q000502:physiology*; D005816:Genetic Complementation Test; D007150:Immunohistochemistry; D008954:Models, Biological; D013552:Swine; D017361:Viral Nonstructural Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D014771:Virion / Q000737:chemistry; D014779:Virus Replication / Q000235:genetics / Q000502:physiology*
chemical_list: D017361:Viral Nonstructural Proteins