Isolation of a fully infectious variant of parvovirus H-1 supplanting the standard strain in human cells.

A variant H-1 virus, designated H-1 dr virus, was isolated from stock of the standard H-1 virus strain propagated in the newborn human kidney cell line NB-E. Molecular cloning and sequence analysis revealed an in-frame deletion at map positions 39 to 41. This deletion affects the open reading frames encoding the nonstructural proteins NS-1 and NS-2 and the untranslated leader sequence of the R3 transcripts encoding the capsid proteins. In addition, H-1 dr virus harbors a 58-nucleotide duplication inboard from the right-hand terminal palindrome. Internal deletions and terminal reiterations are hallmarks of H-1 virus type I variants that typically are defective interfering particles. Indeed, H-1 dr virus was found to progressively supplant the standard strain in serially coinfected NB-E cell cultures. However, H-1 dr virus differed from previously described type I variants in its full infectivity, as was apparent from its ability to give yields of replication and progeny virus production that were similar to those of the standard virus strain in NB-E cells. Hence, the interference of H-1 dr virus in the propagation of standard H-1 virus in coinfected cells was not accompanied by a drop in the titer of infectious virus. Moreover, H-1 dr virus proved to induce the same pathogenic effects in newborn hamsters as the standard virus strain did.

NF kappa B upstream regulatory sequences of the HIV-1 LTR are involved in the inhibition of HIV-1 promoter activity by the NS proteins of autonomous parvoviruses H-1 and MVMp.

To investigate parvoviral interference with human immunodeficiency virus type 1 (HIV-1) in human cells that are normally susceptible to HIV-1 infection, nonstructural (NS) proteins of the parvoviruses H-1 virus and minute virus of mice were studied for their effect on the activity of the HIV-1 promoter in a variety of CD4+ cells. Transient cotransfection assays revealed a reduced HIV-1 promoter activity in the presence of parvoviral NS proteins. Stimulation of the HIV-1 promoter by phorbol 12-myristate 13-acetate (PMA) led to an increase in its sensitivity to NS-induced suppression. The inhibitory effect of NS polypeptides depended, at least in part, on the presence of the NF kappa B motifs of the HIV-1 long terminal repeat, suggesting an interaction of the parvoviral products with PMA-inducible cellular factors binding to these elements of the HIV-1 promoter.