Spread of Oropouche virus into the central nervous system in mouse.

Rodrigo Santos,Eurico Arruda,Lézio Bueno-Júnior,Rafael Ruggiero,Maria Silva,Flávia Paula,Vani Correa,Mariana Almeida

doi:10.3390/v6103827

Rodrigo Santos, Eurico Arruda + Show 6 more

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https://doi.org/10.3390/v6103827

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Abstract

Oropouche virus (OROV) is an important cause of arboviral illness in Brazil and other Latin American countries, with most cases clinically manifested as acute febrile illness referred to as Oropouche fever, including myalgia, headache, arthralgia and malaise. However, OROV can also affect the central nervous system (CNS) with clinical neurological implications. Little is known regarding OROV pathogenesis, especially how OROV gains access to the CNS. In the present study, neonatal BALB/c mice were inoculated with OROV by the subcutaneous route and the progression of OROV spread into the CNS was evaluated. Immunohistochemistry revealed that OROV infection advances from posterior parts of the brain, including the periaqueductal gray, toward the forebrain. In the early phases of the infection OROV gains access to neural routes, reaching the spinal cord and ascending to the brain through brainstem regions, with little inflammation. Later, as infection progresses, OROV crosses the blood-brain barrier, resulting in more intense spread into the brain parenchyma, with more severe manifestations of encephalitis.

Highlights

Oropouche virus (OROV), of the family Bunyaviridae, genus Orthobunyavirus, serogroup Simbu, is an important causative agent of arboviral febrile illness in Brazil
In order to evaluate central nervous system (CNS) involvement during experimental infections that most closely resemble natural routes of infection, we have developed experimental models inoculated by the subcutaneous route, both in neonatal mice and hamsters [10,11]
In animals euthanized three to four days after infection, OROV antigen was found in 7 of 12 mice, and in all 7 animals OROV antigen was detected throughout the brainstem

Summary

Introduction

Oropouche virus (OROV), of the family Bunyaviridae, genus Orthobunyavirus, serogroup Simbu, is an important causative agent of arboviral febrile illness in Brazil. Those studies revealed that the OROV experimental inoculation of hamsters induces systemic infection with development of paralysis and death in roughly one third of the animals, along with conspicuous involvement of the liver and brain as target organs [11]. Eleven animals were euthanized 3 or 4 days post-infection (dpi) regardless of the presence of signs of disease, to evaluate progression of the involvement of the infection kinetics and the route of OROV infection.

Results

Conclusion