LARGE-POPULATION PASSAGES OF VESICULAR STOMATITIS-VIRUS IN INTERFERON-TREATED CELLS SELECT VARIANTS OF ONLY LIMITED RESISTANCE

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 vi ral yield in standard infections. Analysis of viral fitness (overall r eplicative ability measured in direct competition with a reference wil d-type VSV) after 21 passages in IFN-treated cells showed only a limit ed increase or no increase in fitness, compared with the greater incre ase upon parallel passage in cells not treated with IFN-alpha. However , this limited increase in fitness was more pronounced when competitio n assays were carried out with IFN-alpha-treated cells, suggesting the selection of VSV populations with a low level of resistance to IFN-al pha. Thus, despite the extensively documented capacity of VSV to adapt to changing environments, the antiviral state induced by IFN-alpha im poses adaptive constraints on VSV which are not readily overcome.