Susceptibility of human cells to killing by the parvoviruses H-1 and minute virus of mice correlates with viral transcription

Abstract

Human fibroblasts and epithelial cells differing in their susceptibility to killing by the autonomous parvoviruses H-1 and minute virus of mice were compared for their capacity to express viral mRNAs and proteins. The transition from a parvovirus-resistant to a parvovirus-sensitive phenotype correlated with a proportional increase in the production of the three major viral transcripts and of structural and nonstructural proteins. In contrast, cell sensitization to parvovirus could not be correlated with detectable changes in virus uptake, intracellular localization of gene products, stability of viral mRNAs, or phosphorylation of viral nonstructural polypeptides. Moreover, the H-1 virus-sensitive keratinocyte line studied did not sustain a greater level of viral DNA amplification than its resistant derivative. Therefore, the differential susceptibility of the human cells tested to parvovirus infection appears to be mainly controlled at the level of transcription of the viral genome. Parvoviral gene expression could not be elevated by increasing the input multiplicity of infection in either of the cell systems analyzed. Together, these data suggest that a cellular factor(s) regulating parvoviral transcription may be modulated by oncogenic transformation or by differentiation, as both features have been shown to affect cell susceptibility to parvoviruses.

Parvovirus H‐1 infection of human glioma cells leads to complete viral replication and efficient cell killing

“…Parvovirus H‐1 infection is known to inhibit the growth and jeopardize the survival of a number of in vitro ‐transformed or tumor‐derived human and rodent cell lines under conditions in which it does not lead to substantial cytocidal changes in untransformed cells 20, 25, 26, 27, 28, 29, 30. In laboratory animals, H‐1 virus is able to inhibit the formation or growth of tumors, and this oncosuppression is thought to result, at least in part, from virus‐induced oncolysis 20, 21, 46.…”

“…Autonomous parvoviruses were shown to preferentially kill in vitro transformed and tumor‐derived human and rodent cell lines, while limited‐to‐no cytocidal action was observed in nontransformed cells 25, 26, 27, 28, 29, 30. This selective oncolytic effect could also be seen in short‐term cultures of human breast and liver carcinoma cells vs. their corresponding normal counterparts 31, 32.…”

Oncolytic viruses for therapy of malignant glioma

“…Парвовирус крыс Н1 (H1-PV) принадлежит к семейству Parvoviridae. Вирус не имеет оболочки, его геном представлен линейной одноцепочечной ДНК [58]. Репликация вируса происходит в ядре клетки-хозяина и строго зависит от фазы клеточного цикла (репликация вируса возможна только в S-фазе) [59].…”

A Heterogeneous Nuclear Ribonucleoprotein A/B-Related Protein Binds to Single-Stranded DNA near the 5′ End or within the Genome of Feline Parvovirus and Can Modify Virus Replication

“…Autonomous parvoviruses have genomes of about ϳ5,000 nucleotides (nt) of single-stranded (ssDNA) DNA which encode two genes and as few as four proteins, and they depend on the host cell for most of their replicative and metabolic additional functions (15,16), while the adeno-associated viruses (AAV) of the genus Dependovirus also require functions supplied by helper viruses, including adenoviruses or herpesviruses (5). Successful parvovirus replication depends on the mitotic and transformed state of the cell, as well as on its specific differentiated phenotype and host of origin (13,14).…”