Ectopic expression of H-1 parvovirus NS1 protein induces alterations in actin filaments and cell death in human normal MRC-5 and transformed MRC-5 SV2 cells.
When grown in human cell lines, oncolytic H-1 parvovirus (H-1PV) replication preferentially occurs in transformed cells, which ultimately die upon infection. H-1PV-induced cytotoxicity is mainly due to P4 promoter-driven NS1 protein expression. Infection of untransformed cells generally does not induce deleterious effects because the P4 promoter is not activated. Here, we show that ectopic CMV-driven NS1 protein expression in normal human MRC-5 cells results in alterations of actin filaments and cell death, and both effects are prevented by a serine 473 mutation. The same substitution preserves actin filaments of transfected MRC-5 SV2 cells, that are MRC-5 transformed counterparts, but does not impair NS1-induced cytotoxicity.
Wizla
Pierre
P
UMR 8161, CNRS, Institut de Biologie de Lille, 1 rue du Professeur Calmette, BP 447, 59021, Lille Cedex, France. pwizla@me.com
Begue
Agnès
A
Loison
Ingrid
I
Richard
Audrey
A
Caillet-Fauquet
Perrine
P
Stéhelin
Dominique
D
D000199:Actins / Q000378:metabolism*; D016923:Cell Death; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D052661:H-1 parvovirus / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D011401:Promoter Regions, Genetic; D014162:Transfection; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000502:physiology*
D000199:Actins; C106202:NS1 protein, parvovirus; D017361:Viral Nonstructural Proteins