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

Abstract

Mutants (ts21, rev21, and rec21w) 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; ts21 (ts, att, mts+, mgc+); rev21 (ts, att, mts, mgc+) or (ts+, att, mts+, mgc); and rec21w (ts+, att, mts+, mgc+). Inoculation of 2.0 x 10(4) 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 rec21w-infected mice than in wt-infected mice, and almost absent in ts21- and rev21-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 rec21w-infected mice, virus titer in the target organs was almost equivalent to that of wt-infected mice. The growth characteristic of rec21w in the liver was also similar to that of wt. Nevertheless, damage to the organs by rec21w was less than that by wt. Comparison of the phenotypic characteristics between rec21w and wt demonstrated that att affects the ability of MCMV to induce the organ damage without affecting viral growth. Similar comparison between ts21 and rec21w revealed that ts affects the growth of MCMV in most organs.