Influence of adeno-associated virus on adherence and growth properties of normal cells

Abstract

It has been shown previously that infection of newly established cell cultures from malignant human tumors with adeno-associated parvovirus type 2 or type 5 results in growth arrest and cell death. Here we report that the additionally observed antiproliferative effect on diploid human fibroblasts is transient and is connected to a reduced number of cells in S phase. Progression through the cell cycle is disturbed either in GO/G1 or at the G1/S boundary, but an additional arrest in G2 cannot be excluded. DNA synthesis and cell proliferation are resumed when cells are recultured after loosening of cell-matrix adhesions by trypsin treatment. In contrast, they are not resumed by solely providing growth factors via higher amounts of fetal calf serum. The results suggest that cell adherence is altered in adeno-associated parvovirus-infected human embryo fibroblasts.

Parvovirus H‐1 inhibits growth of short‐term tumor‐derived but not normal mammary tissue cultures

“…A parallel can be drawn between this work and recent observations showing that the defective AAV2 and AAV5 parvoviruses interfere with the growth of non-established cell cultures derived from human carcinomas and melanomas (Bantel-Schaal, 1990). The proliferation of normal human fibroblasts was also inhibited by AAV, but only transiently, since it appeared to resume at a normal rate after sub-culture (Winocour et al, 1988;Bantel-Schaal, 1990).…”

“…On the other hand, direct parvovirus/tumor-cell interactions may also participate in oncosuppression. In particular, direct perturbation of the cellular metabolism was attributed to the terminal sequences of parvoviral DNA (Cotmore and Tattersall, 1987;Berns, 1990). Moreover, the intracellular accumulation of the viral regulatory protein NS-1 was found to be toxic for transformed cells (Caillet-Fauquet et al, 1990).…”

“…In particular, systems representative of natural human cancers should be tested, in preference to human cell lines that may drift during their establishment in vitro. Along these lines, it was recently shown that AAV-2 and AAV-5 inhibited the growth of human melanoma and vaginal carcinoma cells, yet these viruses also transiently affected the proliferation of normal foreskin fibroblasts (Winocour et al, 1988;Bantel-Schaal, 1990). As far as autonomous parvoviruses are concerned, a preliminary report indicated that H-1 virus may inhibit human hepatoma-cell growth, without any significant effect on the proliferation of fibroblasts and para-hepatoma normal cells (Wanmin et al, 1989).…”

Respiratory infections of the human bocavirus

“…Until HBoV was discovered, parvovirus B19 was the sole human parvovirus, which can hardly be cultured in in vitro cell cultures, likely because it strongly depends on the optimal cell cycle phase. [4][5][6][7][8][9][10][11][12][13] This latter fact hampered the development of potent and specific antivirals, tenacity studies, and the development of disinfectants active against human parvoviruses as surrogate pathogens with animal pathogenicity were used. The discovery of HBoV led to a couple of molecular findings that are of major general interest for the human parvovirus biology and clinics.…”

Carcinogen‐induced accumulation of adeno‐associated parvovirus dna is transient as a result of two antagonistic activities that both require De Novo protein synthesis

“…The author thanks Dr. H. zur Hausen for encouraging Schaal and Stohr, 1992), thus influencing cellular metabolism discussions and Dr. H. Delius for valuable advice and critical (Ben-Ze'ev ef aZ.. 1980: Camoisi andMedrano. 1983) the reading of the manuscriot.…”