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Published on: June 14, 2020
Persistent measles virus infection of mouse neural cells lacking known human entry receptors
H Abdullah1, J A P Earle, T A Gardiner
1Queen's University Belfast, School of Medicine, Dentistry and Biomedical Sciences, Centre for Infection and Immunity, Belfast, UK.
Aims:
Infection of the mouse central nervous system with wild type (WT) and vaccine strains of measles virus (MV) results in lack of clinical signs and limited antigen detection. It is considered that cell entry receptors for these viruses are not present on murine neural cells and infection is restricted at cell entry.
Methods:
To examine this hypothesis, virus antigen and caspase 3 expression (for apoptosis) was compared in primary mixed, neural cell cultures infected in vitro or prepared from mice infected intracerebrally with WT, vaccine or rodent neuroadapted viruses. Viral RNA levels were examined in mouse brain by nested and real-time reverse transcriptase polymerase chain reaction.
Results:
WT and vaccine strains were demonstrated for the first time to infect murine oligodendrocytes in addition to neurones despite a lack of the known MV cell receptors. Unexpectedly, the percentage of cells positive for viral antigen was higher for WT MV than neuroadapted virus in both in vitro and ex vivo cultures. In the latter the percentage of positive cells increased with time after mouse infection. Viral RNA (total and mRNA) was detected in brain for up to 20 days, while cultures were negative for caspase 3 in WT and vaccine virus infections.
Conclusions:
WT and vaccine MV strains can use an endogenous cell entry receptor(s) or alternative virus uptake mechanism in murine neural cells. However, viral replication occurs at a low level and is associated with limited apoptosis. WT MV mouse infection may provide a model for the initial stages of persistent MV human central nervous system infections.
Insights
Wild type (WT) and vaccine measles virus (MV) strains infect mouse neural cells using unknown entry mechanisms, replicating at low levels without significant apoptosis. This offers a model for persistent MV central nervous system infections.
Area of Science:
- Neurovirology
- Immunology
- Molecular Biology
Background:
- Measles virus (MV) infection of the mouse central nervous system (CNS) typically shows no clinical signs and limited antigen detection.
- This is attributed to the presumed absence of MV cell entry receptors on murine neural cells, restricting infection at the entry stage.
Purpose of the Study:
- To investigate the hypothesis that murine neural cells lack MV cell entry receptors.
- To compare viral antigen and apoptosis in neural cells infected with wild type (WT), vaccine, and neuroadapted MV strains, both in vitro and in vivo.
Main Methods:
- Primary mixed neural cell cultures and intracerebrally infected mice were used.
- Virus antigen, caspase 3 (apoptosis marker), and viral RNA levels were quantified using immunofluorescence and RT-PCR.
Main Results:
- WT and vaccine MV strains infected murine oligodendrocytes and neurons despite lacking known MV receptors.
- Higher viral antigen expression was observed for WT MV compared to neuroadapted strains in both in vitro and ex vivo models.
- Viral RNA was detected in mouse brains for up to 20 days post-infection, with minimal caspase 3 expression indicating limited apoptosis.
Conclusions:
- WT and vaccine MV strains can utilize alternative entry pathways or endogenous receptors in murine neural cells.
- Viral replication is low-level and associated with limited apoptosis.
- WT MV infection in mice presents a potential model for studying early-stage persistent MV CNS infections.
