title: An in-frame deletion in the NS protein-coding sequence of parvovirus H-1PV efficiently stimulates export and infectivity of progeny virions.
abstract: An in-frame, 114-nucleotide-long deletion that affects the NS-coding sequence was created in the infectious molecular clone of the standard parvovirus H-1PV, thereby generating Del H-1PV. The plasmid was transfected and further propagated in permissive human cell lines in order to analyze the effects of the deletion on virus fitness. Our results show key benefits of this deletion, as Del H-1PV proved to exhibit (i) higher infectivity (lower particle-to-infectivity ratio) in vitro and (ii) enhanced tumor growth suppression in vivo compared to wild-type H-1PV. This increased infectivity correlated with an accelerated egress of Del H-1PV progeny virions in producer cells and with an overall stimulation of the viral life cycle in subsequently infected cells. Indeed, virus adsorption and internalization were significantly improved with Del H-1PV, which may account for the earlier appearance of viral DNA replicative forms that was observed with Del H-1PV than wild-type H-1PV. We hypothesize that the internal deletion within the NS2 and/or NS1 protein expressed by Del H-1PV results in the stimulation of some step(s) of the viral life cycle, in particular, a maturation step(s), leading to more efficient nuclear export of infectious viral particles and increased fitness of the virus produced.
authors.affiliation: Program Infection and Cancer, Division Tumor Virology F010, and Institut National de la Santé et de la Recherche Médicale U701, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Weiss
authors.forename: Alexandra
authors.initials: A
authors.lastname: Stroh-Dege
authors.forename: Jean
authors.initials: J
authors.lastname: Rommelaere
authors.forename: Christiane
authors.initials: C
authors.lastname: Dinsart
authors.forename: Nathalie
authors.initials: N
authors.lastname: Salomé
mesh_terms: D002460:Cell Line; D052661:H-1 parvovirus / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity*; D006801:Humans; D010322:Parvoviridae Infections / Q000473:pathology* / Q000821:virology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D053585:Virus Attachment; D053586:Virus Internalization; D057074:Virus Release
chemical_list: D020033:Protein Isoforms; D017361:Viral Nonstructural Proteins