Open AccessFrom nerves to brain to gastrointestinal tract: A time-based study of parrot bornavirus 2 (PaBV-2) pathogenesis in cockatiels (Nymphicus hollandicus)
Author(s) -
Josinaldo Lopes Araújo,
Raquel R. Rech,
J. Jill Heatley,
Jianhua Guo,
Paula R. Giaretta,
Ian R. Tizard,
Aline Rodrigues Hoffmann
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0187797
Subject(s) - proventriculus , pathology , biology , pathogenesis , gastrointestinal tract , spinal cord , lesion , anatomy , lymphatic system , enteric nervous system , peripheral nervous system , immunohistochemistry , histopathology , nervous system , central nervous system , medicine , biochemistry , neuroscience
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.