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Neuropathogenesis induced by rhesus cytomegalovirus in fetal rhesus monkeys (Macaca mulatta)
A F Tarantal1, M S Salamat, W J Britt
1California Regional Primate Research Center, Department of Pediatrics, University of California, Davis 95616-8542, USA. aftarantal@ucdavis.edu
Abstract:
Rhesus cytomegalovirus (RhCMV) infection of rhesus macaques offers opportunities to analyze mechanisms of CMV pathogenesis in a primate species. Four fetal rhesus monkeys were inoculated intraperitoneally with RhCMV early in the second trimester, and pregnancies were terminated by hysterotomy during the third trimester. Three fetuses had evidence of severe CMV disease, including intrauterine growth restriction, ventriculomegaly, microcephaly, lissencephaly, and extensive degenerative changes of the cerebral parenchyma. Histopathologic examination revealed polymicrogyria, gliosis, leptomeningitis, periventricular calcifications, and inclusion-bearing cells. These results demonstrate that the developing macaque brain is susceptible to infection with RhCMV early in the second trimester and that intrauterine infection results in neuropathologic outcomes similar to those observed in humans congenitally infected with CMV.
Insights
Rhesus cytomegalovirus (RhCMV) can severely affect fetal rhesus macaque brains, causing developmental abnormalities and neuropathology similar to human congenital cytomegalovirus (CMV) infection.
Area of Science:
- Primate models of viral pathogenesis
- Developmental neurobiology
- Infectious diseases
Background:
- Rhesus cytomegalovirus (RhCMV) infection in rhesus macaques serves as a valuable model for studying cytomegalovirus (CMV) pathogenesis.
- Congenital CMV infection in humans can lead to severe neurological sequelae.
Purpose of the Study:
- To investigate the neuropathologic effects of RhCMV infection in developing fetal rhesus macaque brains.
- To assess the susceptibility of the second-trimester macaque brain to RhCMV.
Main Methods:
- Four fetal rhesus monkeys were inoculated intraperitoneally with RhCMV early in the second trimester.
- Pregnancies were terminated via hysterotomy in the third trimester for fetal examination.
- Histopathologic analysis was performed on fetal brain tissues.
Main Results:
- Three of the four fetuses exhibited severe congenital CMV disease.
- Observed pathologies included intrauterine growth restriction, ventriculomegaly, microcephaly, lissencephaly, and cerebral parenchymal degeneration.
- Histopathology revealed polymicrogyria, gliosis, leptomeningitis, periventricular calcifications, and inclusion-bearing cells.
Conclusions:
- The developing macaque brain is susceptible to RhCMV infection early in the second trimester.
- Intrauterine RhCMV infection results in neuropathologic outcomes mirroring those seen in human congenital CMV.
- This primate model is crucial for understanding CMV-induced brain damage.