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A rabies virus vampire bat variant shows increased neuroinvasiveness in mice when compared to a carnivore variant

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Abstract

Rabies is one of the most important zoonotic diseases and is caused by several rabies virus (RABV) variants. These variants can exhibit differences in neurovirulence, and few studies have attempted to evaluate the neuroinvasiveness of variants derived from vampire bats and wild carnivores. The aim of this study was to evaluate the neuropathogenesis of infection with two Brazilian RABV street variants (variant 3 and crab-eating fox) in mice. BALB/c mice were inoculated with RABV through the footpad, with the 50% mouse lethal dose (LD50) determined by intracranial inoculation. The morbidity of rabies in mice infected with variant 3 and the crab-eating fox strain was 100% and 50%, respectively, with an incubation period of 7 and 6 days post-inoculation (dpi), respectively. The clinical disease in mice was similar with both strains, and it was characterized initially by weight loss, ruffled fur, hunched posture, and hind limb paralysis progressing to quadriplegia and recumbency at 9 to 12 dpi. Histological lesions within the central nervous system (CNS) characterized by nonsuppurative encephalomyelitis with neuronal degeneration and necrosis were observed in mice infected with variant 3 and those infected with the crab-eating fox variant. However, lesions and the presence of RABV antigen, were more widespread within the CNS of variant-3-infected mice, whereas in crab-eating fox-variant-infected mice, RABV antigens were more restricted to caudal areas of the CNS, such as the spinal cord and brainstem. In conclusion, the results shown here demonstrate that the RABV vampire bat strain (variant 3) has a higher potential for neuroinvasiveness than the carnivore variant.

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Acknowledgements

This study was supported by Sao Paulo Research Foundation (FAPESP), Process number 2015/17807-0. We would like to acknowledge to National Council for Scientific and Technological Development (CNPq) for providing a Master´s Grant to T. H. M. Gamon. We would also like to thank Dr. Mary S. Varaschin for providing the anti-RABV antibody.

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  1. Leonardo Pereira Mesquita and Thais Helena Martins Gamon contributed equally to this manuscript.

Authors and Affiliations

  1. Department of Pathology, School of Veterinary Medicine and Animal Science, University of Sao Paulo, São Paulo, SP, Brazil

    Leonardo Pereira Mesquita, Thais Helena Martins Gamon, Silvia Elena Campusano Cuevas, Dennis Albert Zanatto, Cláudia Madalena Cabrera Mori, Paulo César Maiorka & Enio Mori

  2. Instituto Pasteur de Sao Paulo, Avenida Paulista 393, São Paulo, SP, 01311-000, Brazil

    Karen Miyuki Asano, Willian de Oliveira Fahl, Keila Iamamoto, Karin Correa Scheffer, Samira Maria Achkar & Enio Mori

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  1. Leonardo Pereira Mesquita
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Correspondence to Enio Mori.

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None of the authors declare any conflict of interest with respect to the publication of this manuscript.

Ethical approval

The experiments involving mice were reviewed and approved by the Ethics Committee for the Use of Animals of the School of Veterinary Medicine and Animal Science, University of São Paulo, and by the Instituto Pasteur Institutional Ethics Committee for Animal Experiments.

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Mesquita, L.P., Gamon, T.H.M., Cuevas, S.E.C. et al. A rabies virus vampire bat variant shows increased neuroinvasiveness in mice when compared to a carnivore variant. Arch Virol 162, 3671–3679 (2017). https://doi.org/10.1007/s00705-017-3530-y

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