The effects of human cytomegalovirus persistent infection on the central nervous system of BALB/c mice

Abstract

Objective To investigate the effects of human cytomegalovirus （ HCMV） persistent in-fection on the central nervous system of BALB/c mice.Methods Thirty specific-pathogen-free mice of 6-8 weeks old were randomly divided into three groups including HCMV infected group , inactivated HCMV group and human embryo fibroblast （ HF） control group .Each mouse in the three groups was intraperitoneally inoc-ulated with 1.8 ×107 PFU of HCMV, 1.8 ×107 PFU inactivated HCMV and 1 ×105 HF cells, respectively. All mice were housed in microisolator cages for three months and their behavior and body weight were ob -served.Then three tests including autonomic activities test , Morris Water Maze and step-down passive avoid-ance task were performed on all mice to evaluate the changes of their behavior .Cerebral cortex tissues were collected from all mice to detect HCMV and to conduct polymerase chain reaction （PCR） analysis.Brain tis-sues were stained by HE method to evaluate the pathological damages .Transmission electron microscope was used to observe the ultrastructure of neuron cells and the existence of virus particles .Results （1） The body weight of mice showed no significant differences among the three groups （ P〉0 .05 ） .（ 2 ） The frequency of＆amp;nbsp;autonomic activities were decreases in HCMV infected group in comparison with other two groups , but there was no significant differences among the three groups （P〉0.05）.（3）The place navigation test demonstra-ted that the escape latency of mice from HCMV infected group as well as HF group showed significant differ -ence after training for different periods of time （P〈0.05）.The escape latency of mice with HCMV infection was much longer than that of other two control groups （P〈0.05）, but the differences between two control groups were not significant （P〉0.05）.Compared with the mice in two control groups , the mice in HCMV infected group showed a lower frequency of crossing the quadrant where the platform had been located on pre -vious trials in the probe trial test （P〈0.05）.Moreover, the time of first crossings was also longer than that of mice from two control groups （P〈0.05）.（4）In the learning phase the mice from HCMV infected group showed a high frequency of mistakes in comparison with that from two control groups in step -down passive avoidance task （P〈0.05）.After 24 hours, the frequency of mistakes was decreased in each group , and the differences were significant （P〈0.05）.The latency was very shorter in mice from HCMV infected group than that observed in two control groups （P〈0.05）.（5）The HCMV infection was identified in six mice from HCMV infected group .And the positive HCMV UL83 gene could be only detected in HCMV infected group as indicated by PCR analysis .（6）The pathological changes including cell swelling , loosen cytoplasm, decreased cell layers and vacuolization were observed in the cerebral cortex and hippocampus of mice from HCMV infected group .HCMV-specific intracytoplasmic inclusion bodies and herpes virus like particles were detected by using transmission electron microscope .No obvious abnormalities were observed in two control groups.Conclusion HCMV persistent infection could damage the central nervous system of mice .The au-tonomic activities of mice with HCMV persistent infection were not affected , but the learning and memory ca-pability of them were damaged at some extent . Key words: Human cytomegalovirus; Persistent infection; Mice; Central nervous system