Persistent infection of a gammaherpesvirus in the central nervous system

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.

► Noninvasive bioluminescence imaging of MHV-68 inoculated into the CNS. ► MHV-68 replicates in the brain and is systemically disseminated into the organs. ► Disseminated MHV-68 subsequently establishes latency in the spleen. ► Immunosuppression induces reactivation of MHV-68 from the brain and the spleen. ► MHV-68 may persist inside and outside of the brain once it gains access to the CNS.