Pathogenicity of murine cytomegalovirus for newborn mice: analysis with the attenuated mutants

Summary

Mutants (ts 21, rev 21, and rec 21w) of murine cytomegalovirus (MCMV) with reduced ability to kill newborn mice have been isolated from the Smith strain (wild type; wt). The postulated mutations for these mutants are as follows; a mutation(s) responsible for temperature sensitivity (ts); a mutation(s) responsible for attenuation (att); a mutation(s) which modifies temperature sensitivity (mts); and a mutation(s) responsible for modified growth characteristics (mgc). Genotypes of the mutants have been proposed from their phenotypes; ts 21 (ts, att, mts ⁺ , mgc ⁺); rev 21 (ts, att, mts, mgc ⁺) or (ts ⁺ , att, mts ⁺ , mgc); and rec 21w (ts ⁺ , att, mts ⁺ , mgc ⁺). Inoculation of 2.0×10⁴ plaque forming units (PFU) of wt intraperitoneally into mice resulted in lethal infection accompanying intraperitoneal hemorrhage and pathognomonic changes in the target organs. Such changes were less in rec 21w-infected mice than in wt-infected mice, and almost absent in ts 21- and rev 21-infected mice, on the sixth day after inoculation. The lesser damage to the organs correlated with poor growth of these viruses in the corresponding organs. On the other hand, in the case of rec 21w-infected mice, virus titer in the target organs was almost equivalent to that of wt-infected mice. The growth characteristic of rec 21w in the liver was also similar to that of wt. Nevertheless, damage to the organs by rec 21w was less than that by wt. Comparison of the phenotypic characteristics between rec 21w and wt demonstrated thatatt affects the ability of MCMV to induce the organ damage without affecting viral growth. Similar comparison between ts 21 and rec 21w revealed thatts affects the growth of MCMV in most organs.