Comparable Infection Level and Tropism of Measles Virus and Canine Distemper Virus in Organotypic Brain Slice Cultures Obtained from Natural Host Species.

Brigitta M Laksono,Samira Michels,Georges M G M Verjans,Harry G H Van Engelen,Rory D De Vries,Ivanela Kondova,W Paul Duprex,Diana N Tran,Sham Nambulli,Rik L De Swart

doi:10.3390/v13081582

Abstract

Measles virus (MV) and canine distemper virus (CDV) are closely related members of the family Paramyxoviridae, genus Morbillivirus. MV infection of humans and non-human primates (NHPs) results in a self-limiting disease, which rarely involves central nervous system (CNS) complications. In contrast, infection of carnivores with CDV usually results in severe disease, in which CNS complications are common and the case-fatality rate is high. To compare the neurovirulence and neurotropism of MV and CDV, we established a short-term organotypic brain slice culture system of the olfactory bulb, hippocampus, or cortex obtained from NHPs, dogs, and ferrets. Slices were inoculated ex vivo with wild-type-based recombinant CDV or MV expressing a fluorescent reporter protein. The infection level of both morbilliviruses was determined at different times post-infection. We observed equivalent infection levels and identified microglia as main target cells in CDV-inoculated carnivore and MV-inoculated NHP brain tissue slices. Neurons were also susceptible to MV infection in NHP brain slice cultures. Our findings suggest that MV and CDV have comparable neurotropism and intrinsic capacity to infect CNS-resident cells of their natural host species.

Highlights

Measles virus (MV) and canine distemper virus (CDV) are enveloped viruses with an unsegmented negative sense single-stranded RNA genome that belong to the familyParamyxoviridae, genus Morbillivirus [1]
We established an organotypic brain slice culture from adult ferrets, dogs, and non-human primates (NHPs), based on protocols described in previous studies [21,22]
We could not assess if CDVinfected carnivore neurons due to the lack of cross-reactive antibodies, we observed MVinfected neurons in NHP brain slices

Summary

Introduction

Measles virus (MV) and canine distemper virus (CDV) are enveloped viruses with an unsegmented negative sense single-stranded RNA genome that belong to the familyParamyxoviridae, genus Morbillivirus [1]. Measles virus (MV) and canine distemper virus (CDV) are enveloped viruses with an unsegmented negative sense single-stranded RNA genome that belong to the family. MV causes disease in humans and non-human primates (NHPs), while CDV infects a broad range of species, including dogs, raccoons, mustelids, lions, and even macaques [2,3,4,5,6,7]. Case-fatality rates are low, and morbidity and mortality most often result from measles-associated immune suppression [8]. CDV infection in their natural hosts, in contrast, often leads to severe disease, associated with high case-fatality rates [9]. Both viruses are known to cause neurological complications, but CNS infection is strikingly much more frequent in canine distemper than in measles

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Conclusion