Pathogenesis of infection with a virulent allotropic variant of minute virus of mice and regulation by host genotype.
Neonates of various inbred strains of mice expressed three susceptibility phenotypes in response to infection with the lymphocyte-specific variant of minute virus of mice (MVMi). MVMi caused asymptomatic infections in C57BL/6 (B6) mice, lethal infections with intestinal hemorrhage in DBA/2 mice, and lethal infections with renal papillary hemorrhage in BALB/c, SWR, SJL, CBA, and C3H (H) mice. Sequential virus titration, histology, in situ hybridization with a full-length MVMi genomic probe, and immunohistochemistry for viral capsid antigen were used to compare the pathogenesis of MVMi infection in B6 and H mice. Peak infectious virus titers in heart, lung, liver, spleen, kidney and intestine did not differ between strains but brains of B6 mice, unlike H mice, were refractory to infection. Lesions in H mice consisted of renal papillary infarcts and accelerated involution of hepatic erythropoietic foci. No lesions were seen in B6 mice. In situ hybridization and immunohistochemistry indicated that three cell types were primary targets of MVMi; endothelium, lymphocytes, and hepatic erythropoietic precursors. Renal papillary infarcts in H mice were associated with virus replication in endothelial nuclei of the vasa recta. In contrast to the parity of infectious virus titers between strains, fewer cells in target organs of B6 mice were labeled with the MVMi probe then were labeled in H mice and fewer cells expressed viral capsid antigen. These results indicate (a) that the allotropic variants of minute virus of mice may be useful tools to dissect molecular mechanisms of parvovirus virulence, (b) that the virulence of MVMi for neonatal mice does not reside in its lymphotropism, and (c) that genetic susceptibility to lethal MVMi infection may result from overproduction of noninfectious virus products.
Brownstein
D G
DG
Section of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut.
Smith
A L
AL
Jacoby
R O
RO
Johnson
E A
EA
Hansen
G
G
Tattersall
P
P
D000818:Animals; D014644:Genetic Variation; D005838:Genotype; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D051379:Mice / Q000235:genetics*; D008815:Mice, Inbred Strains; D008915:Minute Virus of Mice / Q000235:genetics* / Q000302:isolation & purification; D009693:Nucleic Acid Hybridization; D010322:Parvoviridae Infections / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D014774:Virulence