Different host-cell shutoff strategies related to the matrix protein lead to persistence of vesicular stomatitis virus mutants on fibroblast cells

Acute infection of fibroblastic cell lines by the Indiana strain of vesicul ar stomatitis virus (VSV) usually induces dramatic cytopathic effects and s hutoff of cellular gene expression. We have compared a series of independen t mutants with differences in shutoff induction and found that M was mutate d either in the N-terminus (M51R) or C-terminus (V221F and S226R). Furtherm ore, only double mutants (M mutation and a ts mutation related or not to M) were able to persist on fibroblast cell lines at 39 degreesC. A more detai led investigation of the infection was performed for the mutants T1026, TP3 and G31, differing in their host shutoff effects related to M protein. Vir al activity in persistently infected mouse L-929 and monkey Vero cell lines was followed by viral proteins detection, RNA synthesis throughout infecti on and finally detection of infectious particles. All three mutants cause e xtensive CPE followed by emergence of persistently infected cells on Vero c ells. The same thing is seen on L-929 cells except for T1026 which causes l ittle CPE. Taken together, the results form a basis of further studies to c larify how various viral and cellular factors interact in the establishment of a persistent infection by VSV mutants. (C) 2001 Elsevier Science B.V. A ll rights reserved.