Reevaluation of the virulence of prototypic strain 15 of pneumonia virus of mice.

Prototypic strain 15 of pneumonia virus of mice (PVM) has been described as being nonpathogenic in mice, in contrast to the mouse-passaged, highly virulent strain J3666. Previous sequence analysis also indicated that strain 15 encodes an attachment G protein that is truncated at the amino terminus, which for the amino terminally anchored protein deletes the cytoplasmic tail. However, we found that PVM strain 15 obtained from the American Type Culture Collection was highly virulent in mice and was essentially indistinguishable on that basis from strain J3666. Sequence analysis showed that this preparation of virus encodes a G protein with an intact cytoplasmic tail: the truncated predicted protein in the previous sequence appeared to be due to a single nucleotide insertion that disrupted the upstream end of the open reading frame and shifted the translational start site to the next downstream AUG. Taken together, the two studies indicate that strain 15 is an inherently virulent strain but that a nonpathogenic variant that was generated during passage in vitro and encodes a truncated G protein exists. Interestingly, the majority sequence of strain J3666 was found to encode a G protein with an extended cytoplasmic tail, suggesting that there is the potential for considerable plasticity in the cytoplasmic tail of the G protein of PVM.