Shedding risk with intracerebral inoculation of theiler's murine encephalomyelitis virus: Informing a risk assessment

Abstract

Theiler's murine encephalomyelitis virus (TMEV) is a naturally occurring enteric infection, easily passed from mouse to mouse in communal housing. However, TMEV is often inoculated intracerebrally (IC) to produce a mouse model of multiple sclerosis (MS). It has long been accepted that maintaining colonies of IC-infected mice within laboratory animal facilities poses a risk of spreading infection from mouse to mouse via the fecal-oral route as well as contaminated equipment or personnel. Interestingly, the extent of virus shedding from IC-inoculated mice has not been investigated, although several publications have remarked on the lack of virus in the peripheral body of this MS mouse model. Viral shedding, thus infectivity, would require that TMEV escape the central nervous system (CNS) and be found in bodily secretions. We hypothesized that if the virus can escape the CNS, it would be found circulating within blood or other secretions postinjection (PI), after the blood-brain barrier has been experimentally breached. The data presented show no TMEV RNA was found in the serum, saliva, or feces during the acute and chronic infection stages, although all subjects were positive for TMEV RNA in the CNS. These results, in conjunction with published anecdotal evidence, suggest that mice IC-inoculated with TMEV are not contagious, and thus a relaxation of containment methods is warranted. This report is an example of a collaborative effort between biosafety and research professionals to identify and collect scientifically relevant data to inform a risk assessment.