The tdCE and hrCE phenotypes: host range mutants of vesicular stomatitis virus in which polymerase function is affected.

Conditional host range mutants of VSV New Jersey (designated tdCE mutants), which multiplied at 31° and 39°C in BHK-21 cells but only at 31° C in chick embryo (CE) cells, were isolated at a higher frequency than conventional ts mutants after 5-fluorouracil mutagenesis. Three types of tdCE mutant could be distinguished by their degree of temperature-sensitivity in other avian cells. Non-conditional host range mutants (hrCE), which failed to multiply in CE cells at both 31° and 39°C, were isolated rarely. The hrCE mutants also failed to produce plaques on MDBK cells.Temperature-shift experiments showed that the host restriction operated early in the viral growth cycle. Nevertheless, pseudotypes of Chandipura virus with envelopes supplied by tdCE or hrCE mutants were not restricted in CE cells, indicating that restriction did not occur at the cell surface. This was consistent with the observation of the in vitro temperature-sensitivity of the virion polymerase of two of the three types of tdCE mutant and the hypothesis that the host range phenotype was determined by host factors which interacted with the virion polymerase (Szilágyi and Pringle, 1975).Comparison of tdCE and hrCE mutants in other cultured cells did not reveal any association of conditional temperature-sensitivity with species of origin, degree of transformation, time in culture, chronic infection with cytoplasmic (RS virus) or nuclear (ALV) RNA viruses, or morphological type. The tdCE mutants, however, tended to be temperature-sensitive in the embryonic cells of some species. The differentiation of pluripotent murine embryonal carcinoma cells to embryoid bodies was accompanied by a decrease in restrictiveness.These results suggest that several host factors may interact with the VSV polymerase, and that the absence of these factors at certain stages of differentiation may have a protective effect.