From nerves to brain to gastrointestinal tract: A time-based study of parrot bornavirus 2 (PaBV-2) pathogenesis in cockatiels (Nymphicus hollandicus).

Jeann Leal De Araujo,J Jill Heatley,Paula R Giaretta,Aline Rodrigues-Hoffmann,Jianhua Guo,Ian Tizard,Raquel R Rech,Jens H Kuhn

doi:10.1371/journal.pone.0187797

Jeann Leal De Araujo, J Jill Heatley + Show 6 more

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https://doi.org/10.1371/journal.pone.0187797

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Journal: PloS one	Publication Date: Nov 9, 2017
Citations: 23	License type: CC BY 4.0

Affiliation: Texas A&M University

Abstract

Parrot bornaviruses (PaBVs) are the causative agents of proventricular dilatation disease, however key aspects of its pathogenesis, such as route of infection, viral spread and distribution, and target cells remain unclear. Our study aimed to track the viral spread and lesion development at 5, 10, 20, 25, 35, 40, 60, 80, 95 and 114 dpi using histopathology, immunohistochemistry, and RT-PCR. After intramuscular inoculation of parrot bornavirus 2 (PaBV-2) in the pectoral muscle of cockatiels, this virus was first detected in macrophages and lymphocytes in the inoculation site and adjacent nerves, then reached the brachial plexus, centripetally spread to the thoracic segment of the spinal cord, and subsequently invaded the other spinal segments and brain. After reaching the central nervous system (CNS), PaBV-2 centrifugally spread out the CNS to the ganglia in the gastrointestinal (GI) system, adrenal gland, heart, and kidneys. At late points of infection, PaBV-2 was not only detected in nerves and ganglia but widespread in the smooth muscle and/or scattered epithelial cells of tissues such as crop, intestines, proventriculus, kidneys, skin, and vessels. Despite the hallmark lesion of PaBVs infection being the dilation of the proventriculus, our results demonstrate PaBV-2 first targets the CNS, before migrating to peripheral tissues such as the GI system.

Highlights

Described in the late 1970s as a disease of large psittacine birds, and originally named “macaw wasting syndrome”, proventricular dilatation disease (PDD) is a fatal and important disease of psittacine birds worldwide, its cause remained obscure for many decades [1, 2].In 2008, two independent studies identified a group of enveloped, non-segmented, negative sense single-stranded RNA viruses of the Bornaviridae family as the cause of PDD [3, 4]
Time-based study of Parrot bornaviruses (PaBVs) infection in cockatiels diverse group of viruses [5,6,7,8,9,10]. The discovery of this high genetic variability of avian bornaviruses associated with the identification of the Variegated squirel bornavirus 1 (VSBV-1), caused an important rearrangement in the monogeneric family Bornaviridae, which was reorganized in 2015 to incorporate 8 distinct species of mammalian, reptile and avian, besides unclassified and unassigned bornaviruses [11]
PaBV-2 reached the brachial plexus, and centripetally extended through the dorsal root ganglia to the spinal cord, which was followed by the invasion of the brain

Summary

Introduction

In 2008, two independent studies identified a group of enveloped, non-segmented, negative sense single-stranded RNA viruses of the Bornaviridae family as the cause of PDD [3, 4]. Time-based study of PaBV infection in cockatiels diverse group of viruses [5,6,7,8,9,10] The discovery of this high genetic variability of avian bornaviruses associated with the identification of the Variegated squirel bornavirus 1 (VSBV-1), caused an important rearrangement in the monogeneric family Bornaviridae, which was reorganized in 2015 to incorporate 8 distinct species of mammalian, reptile and avian, besides unclassified and unassigned bornaviruses [11]. PaBV-6 and PaBV-8 remain unclassified [12]

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