A mouse model of congenital human cytomegalovirus infection that induces liver damage in fetus / 中华传染病杂志

ABSTRACT

Objective To define that human cytomegalovirus (HCMV) can cross the placenta of the Balb/c mice and induce liver damage in developing fetus. Methods HCMV AD169 (6.0 logTCID 50 , 3.0 logTCID 50 , 1.5 logTCID 50 per mouse respectively) was injected into the peritoneum of mice (half of mice were female) when they were about 10 weeks old (weight 25 30g). Then, these mice were paired to mate. Fetus on day about to give birth was removed from the uterus and liver was obtained for virus isolation, pathological studies, examination of the viral DNA positive cells by in situ hybridization using digoxigenin labelled HCMV DNA oligonucleotide probe. Results HCMV could be isolated from the supernatant of tissues; HCMV DNA was found by PCR in supernatant of cell culture with CPE; the presence of viral DNA sequence in hepatocytes was confirmed by in situ hybridization; pathological changes in liver consist of swollen cytoplasm and destroyed nuclei of hepatocytes and distinct intranuclear inclusion in hepatocytes with a cellular infiltrates of predominantly phagocytic cells. All above were found more obviously in fetal mouse liver tissues from the group inoculated with 6.0 log TCID 50 HCMV AD169 as compared with 3.0 log TCID 50 group. In contrast, these positive results couldn't be well found in 1.5 log TCID 50 group. Nothing could be found in normal controls. Conclusions Our research suggests that primary maternal HCMV infection during pregnancy could induce congenital infection in fetus by transplacental transmission and induce fetal liver damage. The mouse model will provide the basis for the study on pathogenesis of congenital HCMV infection in liver and the development of prevention, diagnosis and antiviral agents for congenital HCMV infection in human being.