Differentiation of Closely Related Cells by a Variant of Poliovirus, Type 2, Mef1 Strain

Abstract

PLATES 41 AND 42(Received for publication, June 27, 1959) The conceptual and technical problems associated with latent viral infections have been summarized in recent reviews (1-3) from quite different points of view. Investigation of persistent infection by viruses of mammalian cells in culture has failed to disclose the anticipated occurrence of a lysogenic-like relationship. Numerous studies (4-12) have revealed, instead, a much more complex dynamic equilibrium which permits cells and virus to multiply simultaneously. Since it may not be too fruitful to insist that a lysogenic relationship must constitute a phase of mammalian cell-virus interaction, future experimental design should be more profitable if it takes into accord the multiple phenomena known to be operative. Although substantial progress has been made in establishing some of the factors that determine the nature of cellular susceptibility or resistance to mammalian virus infection (13), its applicability to the "non-cytopathogenic" virus-cell relationship has not been evaluated.Thus, in the case of "moderate" or "temperate" mammalian viruses the basis for the nature of cellular resistance to viral infection and ensuing cytopathogenicity has not been characterized within the framework of classical concepts (14).Experiments which provided an experimental system that appeared to be satisfactory for such studies (15) are the subject of this report which describes the interaction between a variant of pollovirus, Type 2, MEFx strain and a spectrum of primate cell lines. The reaction between this virus and HeLa cells appears to be particularly suitable because of the: (a) relative thermal stability of virus; (b) sharp differential cytopathogenicity of virus for closely related cells; (c) availability of a number of genetic markers for virus including animal and cell culture hosts; (d) simultaneous serial propagation of both virus and cells without resort to the protective effect of homotypic antiserum; (e) observed stability of the virus-cell relationship over a period of 4 years (16).

Changing Viral Susceptibility of a Human Cell Line in Continuous Cultivation

“…Furthermore, in the case of swine influenza virus, adaptation or selection of virus as well as change in the cell is also necessary for the establishment of a host-parasite relationship productive of infective virus. This specificity of ceU-virus relationship is reminiscent of similar specificity manifested with a type 2 poliovirus variant and a HeLa clone with respect not to multiplication but to the inducibility of CPE (34).…”

“…That cells in continuous culture may change in their susceptibility to the effects of viral infection is not a new observation (31)(32)(33)(34)(35). However, previous studies have delineated either: (a) the acquisition of resistance by cells surviving exposure to virus (31), or (b) a varying degree of resistance to viral cytopathic effect of derived cell clones (32)(33)(34)(35), or (c) variation in production of virus by clonal variants (35). The evidence in the present paper appears to be unprecedented in demonstrating a qualitative change in cellular viral susceptibility from a complete incapacity to produce infective virus to acquisition of this ability.…”

Effect of Triiodothyronine on Cells and on Their Response to Infection by Polioviruses

“…Polioviruses. The origin (Murphy and Armstrong, 1959) and characteristics of the cytopathic and submoderate mutants of type 2 poliovirus were reported (Murphy and Wisner, 1962).…”

“…The results (Table 5) showed that HeLa-S3 and Chang cells remained resistant to the cytopathicity of submoderate poliovirus (Murphy and Armstrong, 1959). In one experiment, an attempt was made to overcome the resistance of Chang cells to infection by submoderate poliovirus by increasing 100-fold the virus inoculum.…”

“…Although the effects of a variety of hormones on the replication of viruses in cell cultures were reported (Kilbourne, 1957;Likar and Wilson, 1959;Stewart, 1960), attempts to induce with steroid hormones a cytopathic response of HeLa cells to infection by hepatitis viruses thought to be present in clinical materials (Franklin, 1960) were not successful. Because the delicate balance between cytopathic and noncytopathic response of cell cultures to infection by submoderate poliovirus (Murphy and Armstrong, 1959;Murphy and Landau, in press) could be exploited, a study was made of the influence of L-3,3', 5-triiodothyronine (T3) on cellular response to infection. T3 was used because it is more active than thyroxine (Barker, 1956;Michel and Pitt-Rivers, 1957) on cell metabolism and membrane permeability (Lehninger and Ray, 1957;Tapley and Cooper, 1956).…”