THE VARIOUS SENDAI VIRUS C-PROTEINS ARE NOT FUNCTIONALLY EQUIVALENT AND EXERT BOTH POSITIVE AND NEGATIVE EFFECTS ON VIRAL-RNA ACCUMULATION DURING THE COURSE OF INFECTION

Recombinant Sendai viruses were prepared which cannot express their C- prime, C, or C-prime plus C proteins due to mutation of their respecti ve start codons ([C-prime-minus], [C-minus] and [double mutant], respe ctively). The [C-prime-minus] and [C-minus] stocks were similar to tha t of wild-type (wt) virus in virus titer and plaque formation, whereas the double-mutant stock had a much-reduced PFU or 50% egg infective d ose/particle ratio and produced very small plaques. Relative to the wt virus infection, the [C-prime-minus] and [C-minus] infections of BHK cells resulted in significantly greater accumulation of viral RNAs, co nsistent with the known inhibitory effects of the C-prime and C protei ns. The double-mutant infection, in contrast, was delayed in its accum ulation of viral RNAs; however, once accumulation started, overaccumul ation quickly occurred, as in the single-mutant infections. Our result s suggest that the C-prime and C proteins both provide a common positi ve function early in infection, so that only the double mutant undergo es delayed RNA accumulation and exhibits the highly debilitated phenot ype, Later in infection, the same proteins appear to act as inhibitors of RNA accumulation. In infections of mice, [C-prime-minus] was found to be as virulent as wt virus whereas [C-minus] was highly attenuated . These results suggest that the C-prime and C proteins cannot be func tionally equivalent, since C can replace C-prime for virulence in mice whereas C-prime cannot replace C.