PATHOGENICITY OF MURINE CYTOMEGALOVIRUS FOR NEWBORN MICE - ANALYSIS WITH THE ATTENUATED MUTANTS

Mutants (ts21, rev21, and rec21w) of murine cytomegalovirus (MCMV) wit h reduced ability to kill newborn mice have been isolated from the Smi th 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) w hich modifies temperature sensitivity (mts); and a mutation(s) respons ible for modified growth characteristics (mgc). Genotypes of the mutan ts 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 ac companying 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 c orrelated with poor growth of these viruses in the corresponding organ s. 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 mic e. The growth characteristic of rec21w in the liver was also similar t o that of wt. Nevertheless, damage to the organs by rec21w was less th an that by wt. Comparison of the phenotypic characteristics between re c21w and wt demonstrated that att affects the ability of MCMV to induc e the organ damage without affecting viral growth. Similar comparison between ts21 and rec21w revealed that ts affects the growth of MCMV in most organs.