Murine gammaherpesvirus-68 infection of and persistence in the central nervous system

Area of Science:

• Virology
• Neuroscience
• Immunology

Background:

• Murine gammaherpesvirus-68 (MHV-68) is a gammaherpesvirus with a history of isolation from mouse brain.
• Gammaherpesviruses are increasingly recognized for their potential to cause neurological disease.
• The neuroinvasive potential of MHV-68 remains incompletely understood.

Purpose of the Study:

• To investigate the capacity of MHV-68 to access, replicate within, and persist in the mouse central nervous system (CNS).
• To characterize the neuropathogenesis of MHV-68 following different routes of infection and reactivation.

Main Methods:

• Intranasal inoculation of MHV-68 in wild-type and type-I interferon receptor knockout mice.
• Direct intracerebral inoculation of MHV-68.
• Intracerebral implantation of MHV-68-infected glial cells.
• Treatment with antiviral thionucleoside analogue.

Main Results:

• Intranasal inoculation generally did not lead to neuroinvasion, except in interferon receptor-deficient mice where perivascular CNS infection was observed.
• Direct intracerebral inoculation resulted in fatal, widespread CNS infection, primarily affecting meningeal, ependymal cells, neurons, oligodendrocytes, glia, and neural progenitor cells.
• Reactivation models showed that implanted infected cells could cause fatal CNS infections, with tropism varying based on implantation site.
• Antiviral treatment allowed survival, with persistent infected cells detected in the brain a year later.

Conclusions:

• MHV-68 exhibits limited neuroinvasiveness via intranasal routes but can cause severe CNS disease upon direct inoculation or reactivation.
• The type-I interferon pathway plays a crucial role in controlling MHV-68 CNS infection.
• MHV-68 can establish persistent infections within the CNS, highlighting its potential as a model for gammaherpesvirus-induced neurological disorders.