Intracerebral Inoculation of Mouse-Passaged Saffold Virus Type 3 Affects Cerebellar Development in Neonatal Mice

Area of Science:

• Virology
• Neuroscience
• Pathogenesis

Background:

• Saffold virus (SAFV), a human cardiovirus, is linked to infant neurological disorders.
• Previous studies showed SAFV infects cerebellar glial cells but not neurons in mice.
• The impact of SAFV infection on cerebellar development remained unclear.

Purpose of the Study:

• To determine the neuropathogenesis of SAFV type 3 in neonatal mouse cerebella.
• To investigate the effects of an in vivo-passaged SAFV strain on the developing brain.
• To establish a neonatal mouse model for studying SAFV neuropathogenicity.

Main Methods:

• SAFV type 3 was passaged multiple times in neonatal mouse cerebella.
• The passaged viral strain's genome and capsid protein mutations were analyzed.
• Molecular modeling was used to predict the impact of mutations on viral structure.
• Neurovirulence and replication of original and passaged SAFV strains were assessed in neonatal mice.
• Histological analysis examined the effects on cerebellar cells, particularly Purkinje cells.

Main Results:

• A passaged SAFV strain exhibited amino acid substitutions in VP2 and VP3 capsid proteins.
• These mutations potentially altered the receptor binding surface dynamics.
• The passaged strain showed increased replication and neurovirulence in neonatal mouse brains.
• Both strains infected glial and neural progenitor cells, affecting Purkinje cell dendrites.
• High titers of the passaged strain led to cerebellar hypoplasia in neonatal mice.

Conclusions:

• Mouse-passaged SAFV significantly impacts cerebellar development in neonatal mice.
• The identified mutations may contribute to increased viral neurovirulence.
• This neonatal mouse model is valuable for elucidating SAFV neuropathogenesis in early life.
• Findings contribute to understanding SAFV as a potential neuropathogenic agent in infants.