title: Large-population passages of vesicular stomatitis virus in interferon-treated cells select variants of only limited resistance.
abstract: Vesicular stomatitis virus (VSV) populations were repeatedly passaged in L-929 cells treated with alpha interferon (IFN-alpha) at levels of 25 U/ml. This IFN-alpha concentration induced a 99.9% inhibition of viral yield in standard infections. Analysis of viral fitness (overall replicative ability measured in direct competition with a reference wild-type VSV) after 21 passages in IFN-treated cells showed only a limited increase or no increase in fitness, compared with the greater increase upon parallel passage in cells not treated with IFN-alpha. However, this limited increase in fitness was more pronounced when competition assays were carried out with IFN-alpha-treated cells, suggesting the selection of VSV populations with a low level of resistance to IFN-alpha. Thus, despite the extensively documented capacity of VSV to adapt to changing environments, the antiviral state induced by IFN-alpha imposes adaptive constraints on VSV which are not readily overcome.
authors.affiliation: Department of Biology, University of California, San Diego, La Jolla, 92093-0116, USA.
authors.forename: I S
authors.initials: IS
authors.lastname: Novella
authors.forename: M
authors.initials: M
authors.lastname: Cilnis
authors.forename: S F
authors.initials: SF
authors.lastname: Elena
authors.forename: J
authors.initials: J
authors.lastname: Kohn
authors.forename: A
authors.initials: A
authors.lastname: Moya
authors.forename: E
authors.initials: E
authors.lastname: Domingo
authors.forename: J J
authors.initials: JJ
authors.lastname: Holland
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D014644:Genetic Variation; D016898:Interferon-alpha / Q000494:pharmacology*; D007739:L Cells; D051379:Mice; D012641:Selection, Genetic; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D016898:Interferon-alpha