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Persistent poliovirus infection of human fetal brain cells
N Pavio1, M H Buc-Caron, F Colbère-Garapin
1Unité de Neurovirologie et Régénération du Système Nerveux, Institut Pasteur, Paris, France.
Abstract:
It has been suggested that poliovirus (PV), the causative agent of poliomyelitis, could persist in surviving patients. We have previously shown that PV can persistently infect some human cell lines in vitro, particularly neuroblastoma cell lines. We report here an ex vivo model in which PV can persistently infect primary cultures of human fetal brain cells. Two mutations involving capsid residues 142 of VP2 and 95 of VP1 were repeatedly selected during the persistent infections. These residues are located in capsid regions known to be involved in interactions between PV and its receptor. During the first week after infection, viral antigens were found in cells of both the neuronal and glial lineages. In contrast, 2 weeks after infection, viral antigens were detected almost exclusively in cells of the neuronal lineage. They were detected predominantly in cells expressing a marker of early commitment to the neuronal lineage, MAP-5, particularly in neuroblasts. Viral antigens were also found in immature progenitors expressing a neuroepithelium marker, nestin, and in cells expressing a marker of postmitotic neurons, MAP-2. The presence of viral antigens in postmitotic neurons suggests that PV can persist in neurons of patients who have survived poliomyelitis.
Insights
Poliovirus can persistently infect human fetal brain cells, particularly neurons, in an ex vivo model. This suggests poliovirus may persist in neurons of patients who have survived poliomyelitis.
Area of Science:
- Neuroscience
- Virology
- Cell Biology
Background:
- Poliovirus (PV), the cause of poliomyelitis, may persist in patients after recovery.
- Previous in vitro studies demonstrated PV's ability to persistently infect human cell lines, especially neuroblastoma cells.
Purpose of the Study:
- To establish an ex vivo model for persistent poliovirus infection in primary human fetal brain cells.
- To investigate the cell types and viral mutations involved in persistent poliovirus infection in the brain.
Main Methods:
- Utilized primary cultures of human fetal brain cells for ex vivo modeling.
- Infected cells with poliovirus and monitored for persistent infection.
- Analyzed viral capsid mutations (VP1, VP2) and identified viral antigens in different neural cell lineages using specific markers (MAP-5, nestin, MAP-2).
Main Results:
- Poliovirus persistently infected primary human fetal brain cell cultures.
- Two specific mutations in VP1 and VP2 capsid residues were consistently selected during persistent infection.
- Initially, viral antigens were found in both neuronal and glial cells, but after two weeks, they were predominantly detected in neuronal lineage cells, including neuroblasts and postmitotic neurons.
Conclusions:
- An ex vivo model demonstrates persistent poliovirus infection in human fetal brain cells.
- The findings suggest that poliovirus can persist in neurons of individuals who have recovered from poliomyelitis.
- Specific capsid mutations are associated with persistent poliovirus infections in neural cells.