Persistent infection of a gammaherpesvirus in the central nervous system

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.

Alpha- and gammaherpesviruses in stranded striped dolphins (Stenella coeruleoalba) from Spain: first molecular detection of gammaherpesvirus infection in central nervous system of odontocetes

“…However, some neurotropism has also been suggested in human gammaherpesviruses [ 46 – 50 ]. Thus, comparing it to clearly neurotropic viruses, another potential route may be via autonomic neurons in the genitals, similar to the route taken by human herpesviruses type 1 and type 2 to reach the spinal cord [ 51 ].…”

“…To our knowledge this is the first report of gammaherpesvirus detection in the central nervous system of dolphins. It has been described that human gammaherpesvirus can be found in healthy human brains [ 47 , 48 ] and Murine gammaherpesvirus 68 was found to be able to cause a persistent infection in mice central nervous system [ 46 ] suggesting a neuroinvasive and neuropersistent potential. This discovery enhances our understanding of herpesvirus infection in cetaceans and brings up many questions that need further investigation about how herpesvirus infection progresses in cetaceans, particularly in the central nervous system, what are the risk factors of such infection and how infection manifests clinically.…”

A Gammaherpesvirus Establishes Persistent Infection in Neuroblastoma Cells

“…Lytic gene expression, DNA replication, and virion production were concomitantly induced after treatment with TPA and sodium butyrate, but they were blocked after treatment with GCV. Taken together, these results suggest that both productive and latent infections may be established in neuroblastoma cells, which may account for persistent infection in the brain of infected mice (Cho et al, 2009;Kang et al, 2012). Because only few cell lines are available to study persistent infection of MHV-68 áå= îáíêç following ÇÉ= åçîç infection, MHV-68 infection in neuroblastoma cells may provide a valuable experimental system to investigate the various aspects of γHV latency by using functional genomics.…”

Murid herpesvirus 4 (MuHV-4, prototype strain MHV-68) as an important model in global research of human oncogenic gammaherpesviruses

“…MHV-68 is being evaluated as a model of EBV infection for use in investigation of the effects of immunomodulatory therapy on herpesvirus pathogen-esis in humans (Aligo et al, 2015a). MHV-68 may persist both inside and outside the central nervous system (CNS) once it gains access to the CNS (Kang et al, 2012). Based on similar pathogenetic properties of MHV-68 and EBV, the mouse model is appropriate for the study of human cerebral EBV infection as a hydrocephalus, meningitis, cerebellitis, focal or diffuse encephalitis and temporal lobe encephalitis (Häusler et al, 2005).…”