Parvovirus replication in normal and transformed human cells correlates with the nuclear translocation of the early protein NS1.

The parvovirus H-1 infection of the normal human diploid fibroblast strain MRC-5 produces a cytopathic effect, but no increase in infectious virus has been observed. Previously, we reported that large amounts of empty capsids are assembled in the nucleus of H-1 infected MRC-5 cells (S. Singer and S. Rhode, in D. Ward and P. Tattersall, ed., Replication of Mammalian Parvoviruses, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y., 1978). The level of viral replicative-form DNA synthesis as shown by metabolic labeling is markedly reduced in these cells. Synthesis of the early protein NS1 is normal or slightly decreased, and the usual amount of the 92,000-molecular-weight (92K) posttranslationally modified NS1 was seen. The second deficient parameter that we have observed in the abortive infection is the nuclear translocation of NS1. In contrast, the simian virus 40-transformed MRC-5 cell line MRC-5 V1 and the simian virus 40-transformed human kidney cell line NB undergo a productive infection by H-1 accompanied by more efficient translocation of NS1 to the nucleus. The results indicate that there is an association between defective translocation of the NS1 rep protein to the nucleus and defective amplification of parvovirus replicative-form DNA. The nuclear translocation of specific proteins seems to be a function that is altered by development or neoplastic transformation.