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Comparative Study
. 2021 Aug 10;13(8):1582.
doi: 10.3390/v13081582.

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  1 , Diana N Tran  1 , Ivanela Kondova  2 , Harry G H van Engelen  3 , Samira Michels  1 , Sham Nambulli  4 , Rory D de Vries  1 , W Paul Duprex  4 , Georges M G M Verjans  1 , Rik L de Swart  1
Affiliations
Comparative Study

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 et al. Viruses. .

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.

Keywords: canine distemper virus; central nervous system; measles virus; morbillivirus; organotypic brain slice culture; pathogenesis; tropism.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Different morphology of morbillivirus-infected cells. Whereas most virus-infected cells (green) were round single cells (left column), cells with different morphology were also observed in CDV-infected dog and ferret, and MV-infected NHP brain slices (middle and right columns).
Figure 2
Figure 2
Microglia, but not astrocytes, in brain slice cultures were susceptible to morbillivirus infection. (A) Representative CDV-infected ferret hippocampal slices at 2 days post-infection (dpi). Some CDV-infected cells (green, arrows) were microglia (Iba1+ cells; yellow), but not astrocytes (GFAP+ cells, red). An Iba1− GFAP− CDV-infected cell (green, arrowhead) was also present. (B,C) Representative ex vivo NHP cortex slices. MV-infected cells (green, arrows) were mainly microglia (yellow), but not astrocytes (red).
Figure 3
Figure 3
Neurons in NHP brain slice cultures were susceptible to MV infection. Representative MV-infected (green) NHP neurons (NeuN+; red) in the olfactory bulb, hippocampal, and cortex slices collected at 3 days post-inoculation.
Figure 4
Figure 4
Oligodendrocytes in NHP brain slice cultures were susceptible to MV infection. Representative MV-infected (GFP+; green) NHP oligodendrocytes (CNPase+; red) in the olfactory bulb, hippocampal, and cortex slices. Olfactory bulb and cortex slices were collected at 3 days post-inoculation (dpi) and hippocampal slice was collected at 4 dpi. In some slices, infected cells that were CNPase− were also present, as represented in the cortex slice (arrowhead).
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