A new study published online in PLOS ONE reveals that primitive human stem cells are resistant to human cytomegalovirus (HCMV), one of the leading prenatal causes of congenital intellectual disability, deafness and deformities worldwide. Researchers from the University of Pittsburgh School of Medicine found that as stem cells and other primitive cells mature into neurons, they become more susceptible to HCMV, which could allow them to find effective treatments for the virus and to prevent its potentially devastating consequences.
"Previous studies have focused on other species and other cell types, but those studies did not evaluate what the cytomegalovirus does to human brain cells," said Vishwajit Nimgaonkar, M.D., Ph.D., professor of psychiatry at the University of Pittsburgh School of Medicine, and senior author of the report. "This study is the first of its kind, and the first to discover that primitive stem cells are actually resistant to HCMV."
Access to cultured human neurons, necessary to understand the pathogenic effects of HCMV, has been limited by difficulties in growing the brain cells in the laboratory. Yet through human-induced pluripotent stem (iPS) cells, researchers were able to overcome this hurdle.
The study authors derived live iPS cells by reprogramming cells called fibroblasts obtained from human skin biopsies. The iPS cells were then induced to mature through several stages into neurons, the primary cells in the brain. The researchers were able to evaluate the patterns of damage caused by HCMV on all these cells.
The research findings suggest:
Human iPS cells do not permit a full viral replication cycle, suggesting for the first time that these cells can resist CMV infection
CMV infection distorts iPS cell differentiation into neurons, and that may be a mechanism by which infected babies develop impairments of brain maturation and intellectual ability
iPS-derived mature neurons are more susceptible to CMV infection and once infected show effects including defective function that have been shown in other animal studies and in other human tissues, and the neurons die a few days after infection lab studies, possibly reflecting the impact of CMV on the human brain