Persistent infection of a gammaherpesvirus in the central nervous system
Hye-Ri Kang1, Hye-Jeong Cho, Sungbum Kim
1Virus-Host Interactions Laboratory, College of Life Sciences and Biotechnology, Korea University, Seoul 136-713, Republic of Korea.
Abstract:
Human gammaherpesvirus infections of the central nervous system (CNS) have been linked to various neurological diseases. Murine gammaherpesvirus 68 (MHV-68), genetically related and biologically similar to human gammaherpesviruses, infects the CNS in laboratory mice. However, viral persistency of MHV-68 has not been studied following CNS infection. In this study, we undertook the noninvasive bioluminescence imaging of a recombinant MHV-68 expressing the firefly luciferase (M3FL) to monitor virus progression after CNS infection. The M3FL virus inoculated in the brain systemically spread to the abdominal area in bioluminescence imaging, which was further confirmed by detection of viral genome and transcripts. The disseminated wild-type virus established latency in the spleen. Moreover, the treatment of the infected mice with CsA induced reactivation of latent MHV-68 from the brain and the spleen. Our results suggest that MHV-68 may persist both inside and outside the CNS once it gains access to the CNS.
Insights
Murine gammaherpesvirus 68 (MHV-68) can persist in the central nervous system (CNS) and spleen after CNS infection in mice. Cyclosporine A treatment reactivated latent MHV-68 from both locations.
Area of Science:
- Virology
- Neuroscience
- Immunology
Background:
- Human gammaherpesvirus infections are associated with neurological diseases.
- Murine gammaherpesvirus 68 (MHV-68) is a model for human gammaherpesviruses and infects the mouse CNS.
- Viral persistence of MHV-68 within the CNS remains uncharacterized.
Purpose of the Study:
- To investigate the persistence and dissemination of MHV-68 following CNS infection.
- To establish a model for studying MHV-68 latency and reactivation in the CNS and periphery.
Main Methods:
- Utilized a recombinant MHV-68 expressing firefly luciferase (M3FL) for noninvasive bioluminescence imaging.
- Monitored virus progression and dissemination after intracranial inoculation in mice.
- Detected viral genome and transcripts to confirm systemic spread and latency.
- Administered Cyclosporine A (CsA) to induce reactivation of latent virus.
Main Results:
- Bioluminescence imaging revealed systemic spread of M3FL from the brain to abdominal organs.
- Viral genome and transcripts confirmed dissemination and establishment of latency in the spleen.
- Latent MHV-68 was successfully reactivated from both the brain and spleen following CsA treatment.
Conclusions:
- MHV-68 can establish persistent infection both within the CNS and systemically outside the CNS after initial CNS entry.
- The spleen serves as a site for MHV-68 latency following CNS infection.
- MHV-68 latency in both CNS and spleen is susceptible to reactivation.
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