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Nyctinomops laticaudatus bat-associated Rabies virus causes disease with a shorter clinical period and has lower pathogenic potential than strains isolated from wild canids

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Abstract

Rabies is a lethal viral disease that can affect a wide range of mammals. Currently, Rabies virus (RABV) in some European and American countries is maintained primarily in wild species. The regulation of viral replication is one of the critical mechanisms involved in RABV pathogenesis. However, the relationship between replication and the pathogenesis of RABV isolated from wild animals remains poorly understood. In the present study, we evaluated the pathogenicity of the street viruses Nyctinomops laticaudatus bat-associated RABV (NYBRV) and Cerdocyon thous canid-associated RABV (CECRV). Infection of mice with NYBRV led to 33% mortality with rapid disease evolution and marked histopathological changes in the CNS. In contrast, infection with CECRV led to 67% mortality and caused mild neuropathological lesions. The proportion of RABV antigen was significantly higher in the cytoplasm of neuronal cells of the cerebral cortex and in the meninges of mice infected with CECRV and NYBRV, respectively. Moreover, the replication rate of NYBRV was significantly higher (p < 0.001) than that of CECRV in neuroblastoma cells. However, CECRV replicated to a significantly higher titer in epithelial cells. Our results indicate that NYBRV infection results in rapid disease progression accompanied by frequent and intense histopathological alterations in the CNS in mice, and in a high replication rate in neuroblastoma cells. Although, CECRV is more pathogenic in mice, it caused milder histopathological changes in the CNS and replicated more efficiently in epithelial cells. Our data point to a correlation between clinical aspects of disease and the replication of RABV in different cell lines.

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Acknowledgements

We would like to thank Karen Myiuki Asano at the Pasteur Institute for providing the mice. This work was supported by Instituto Pasteur, São Paulo, Brazil.

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Authors and Affiliations

  1. Pasteur Institute, Av. Paulista 393, São Paulo, SP, CEP 01311-000, Brazil

    Natalia Langenfeld Fuoco, Elaine Raniero Fernandes, Fernanda Guedes, Sandriana Dos Ramos Silva, Leticia Patricia Guimarães, Nayara Ugeda Silva & Iana Suly Santos Katz

  2. Laboratory of Immunogenetics, Butantan Institute, Av. Vital Brasil 1500, São Paulo, SP, CEP 05503-900, Brazil

    Orlando Garcia Ribeiro

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  1. Natalia Langenfeld Fuoco
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Correspondence to Iana Suly Santos Katz.

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The study protocol was approved by the Committee on the Ethics of Animal Experiments of the Instituto Pasteur of São Paulo. All institutional and national guidelines for the care and use of laboratory animals were followed.

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Fuoco, N.L., Fernandes, E.R., Guedes, F. et al. Nyctinomops laticaudatus bat-associated Rabies virus causes disease with a shorter clinical period and has lower pathogenic potential than strains isolated from wild canids. Arch Virol 164, 2469–2477 (2019). https://doi.org/10.1007/s00705-019-04335-5

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