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Pathogenicity of murine cytomegalovirus for newborn mice: analysis with the attenuated mutants
K Ibusuki1, K Kumura, Y Minamishima
1Department of Microbiology, Miyazaki Medical College, Japan.
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.
Insights
Murine cytomegalovirus (MCMV) mutants show reduced pathogenicity. Attenuation (att) affects organ damage without impacting viral growth, while temperature sensitivity (ts) impairs MCMV growth.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- Murine cytomegalovirus (MCMV) is a pathogen that can cause lethal infections in newborn mice.
- Understanding MCMV virulence factors is crucial for developing effective antiviral strategies.
Purpose of the Study:
- To characterize novel MCMV mutants with reduced pathogenicity.
- To elucidate the roles of temperature sensitivity (ts) and attenuation (att) mutations in MCMV virulence.
Main Methods:
- Isolation and characterization of temperature-sensitive (ts) and attenuated (att) MCMV mutants from the Smith strain (wild type; wt).
- Phenotypic analysis of mutants, including determination of temperature sensitivity (ts), attenuation (att), modified temperature sensitivity (mts), and modified growth characteristics (mgc).
- Inoculation of mice with wild-type and mutant MCMV strains, followed by assessment of survival, organ damage, and viral titers.
Main Results:
- MCMV mutants ts21, rev21, and rec21w exhibited reduced ability to kill newborn mice compared to wild-type MCMV.
- The rec21w mutant showed attenuated virulence, causing less organ damage than wild-type MCMV despite similar viral titers in target organs.
- The ts21 and rev21 mutants displayed significantly reduced organ damage, correlating with poor viral growth in affected organs.
- Attenuation (att) was identified as a factor affecting MCMV's ability to induce organ damage independently of viral growth.
- Temperature sensitivity (ts) was found to impair MCMV growth in most organs.
Conclusions:
- MCMV attenuation is a key determinant of reduced pathogenicity, affecting organ damage without altering viral replication.
- Temperature sensitivity significantly impacts MCMV's growth capacity in host organs.
- These findings provide insights into MCMV virulence mechanisms and potential targets for therapeutic intervention.