Abstract
Human cytomegalovirus infection of the developing fetus is a leading cause of neurodevelopmental disorders in infants and children, leading to long-term neurological sequela in a significant number of infected children. Current understanding of the neuropathogenesis of this intrauterine infection is limited because of the complexity of this infection, which includes maternal immunological responses that are overlaid on virus replication in the CNS during neurodevelopment. Furthermore, available data from human cases are observational, and tissues from autopsy studies have been derived from only the most severe infections. Animal models of this human infection are also limited by the strict species specificity of cytomegaloviruses. However, informative models including non-human primates and small animal models have been developed. These include several different murine models of congenital HCMV infection for the study of CMV neuropathogenesis. Although individual murine models do not completely recapitulate all aspects of the human infection, each model has provided significant information that has extended current understanding of the neuropathogenesis of this human infection. This review will compare and contrast different murine models in the context of available information from human studies of CNS disease following congenital HCMV infections.
Highlights
Perinatal infections caused by human cytomegalovirus (HCMV) are common and include both infections acquired in utero and those acquired in the peripartum period and in early infancy
Clinically significant perinatal infections occur in premature infants who acquire HCMV early in life, most severe HCMV infections and, in particular, those associated with long-term neurodevelopmental sequelae, result from intrauterine transmission of HCMV to the developing fetus
The method which is selected for infection and the timing of infection are both dependent on the context of the individual study, and more importantly, on the specific goals of the study, because it is unlikely that any single murine model can faithfully recapitulate the complexity of mechanisms of diseases associated with congenital HCMV infection
Summary
Perinatal infections caused by human cytomegalovirus (HCMV) are common and include both infections acquired in utero (congenital HCMV) and those acquired in the peripartum period and in early infancy. Findings in infants with symptomatic infections can include dysfunction in multiple organ systems with disordered hepatic function, hematological abnormalities, growth restriction, and perhaps most importantly for long-term outcomes, evidence of CNS damage [4,5] (Table 1). A subset of infants with asymptomatic cCMV infection without clinical evidence of CNS infection can exhibit neurodevelopmental abnormalities, including permanent hearing loss and vestibular dysfunction (Table 1) [7,8]. Efforts to more accurately define mechanisms of CNS disease associated with cCMV infection have relied on small animal models and, less frequently, non-human primate models. Each of these models employs their respective CMV because HCMV and most other mammalian CMVs are exquisitely species-specific. Abnormal neurologic findings(seizures, motor and cognitive deficits; delays in neurodevelopment)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
