Abstract
During rabies virus infections, the minor salivary glands are one of the important organs for virus replication and excretion into the oral cavity. However, details of pathological findings and viral antigen distribution in the minor salivary glands remain poorly understood. In this study, we conducted pathological tests on the tongues of 71 rabid dogs in the Philippines; the minor salivary glands (von Ebner’s glands, lingual glands), circumvallate papilla, autonomic ganglia, and skeletal muscles were evaluated. Inflammatory changes were observed in the von Ebner’s glands of 20/71 dogs, in the circumvallate papilla of 10/71, and in the tongue muscle of 1/71. Conversely, no morphological changes were observed in the lingual glands and autonomic ganglia. Viral antigens were detected via immunohistochemistry-based methods in the cytoplasm of the acinar epithelium in the von Ebner’s glands of all 71 dogs. Virus particles were confirmed in the intercellular canaliculi and acinar lumen via electron microscopy. In the autonomic ganglia, viral antigens were detected in 67/71 rabid dogs. Viral antigens were detected in the taste buds of all 71 dogs, and were distributed mainly in type II and III taste bud cells. In tongue muscle fibers, viral antigens were detected in 11/71 dogs. No virus antigens were detected in lingual glands. These findings suggest that rabies virus descends in the tongue along the glossopharyngeal nerve after proliferation in the brain, and von Ebner’s glands and taste buds are one of the portals of virus excretion into the saliva in rabid dogs.
Similar content being viewed by others
References
World Health Organization (2013) WHO expert consultation on rabies. Second report. World Health Organ Tech Rep Ser 982:1–139
Fooks AR, Banyard AC, Horton DL, Johnson N, McElhinney LM, Jackson AC (2014) Current status of rabies and prospects for elimination. Lancet 384:1389–1399
Banyard AC, Horton DL, Freuling C, Müller T, Fooks AR (2013) Control and prevention of canine rabies: the need for building laboratory-based surveillance capacity. Antivir Res 98:357–364
Prager KC, Mazet JA, Dubovi EJ, Frank LG, Munson L, Wagner AP, Woodroffe R (2012) Rabies virus and canine distemper virus in wild and domestic carnivores in Northern Kenya: are domestic dogs the reservoir? Ecohealth 9:483–498
Dimaano EM, Scholand SJ, Alera MT, Belandres DB (2011) Clinical and epidemiological features of human rabies cases in the Philippines: a review from 1987 to 2006. Int J Infect Dis 15:e495–e499
Hemachudha T, Laothamatas J, Rupprecht CE (2002) Human rabies: a disease of complex neuropathogenetic mechanisms and diagnostic challenges. Lancet Neurol 1:101–109
Boonsriroj H, Manalo DL, Kimitsuki K, Shimatsu T, Shiwa N, Shinozaki H, Takahashi Y, Tanaka N, Inoue S, Park CH (2016) A pathological study of the salivary glands of rabid dogs in the Philippines. J Vet Med Sci 78:35–42
Charlton KM, Casey GA, Campbell JB (1983) Experimental rabies in skunks: mechanisms of infection of the salivary glands. Can J Comp Med 47:363–369
Charlton KM, Casey GA, Webster WA (1984) Rabies virus in the salivary glands and nasal mucosa of naturally infected skunks. Can J Comp Med 48:338–339
Gargiulo AM, Ceccarelli P, Dall’Aglio C, Pedini V (1995) Ultrastructure of bovine von Ebner’s salivary glands. Ann Anat 177:33–37
Hand AR (1970) The fine structure of von Ebner’s gland of the rat. J Cell Biol 44:340–353
Hand AR, Pathmanathan D, Field RB (1999) Morphological features of the minor salivary glands. Arch Oral Biol 44:S3–S10
Ibira Y, Yokosuka H, Haga-Tsujimura M, Yoshie S (2013) Occurrence of gustducin-immunoreactive cells in von Ebner’s glands of guinea pigs. Histochem Cell Biol 140:567–574
Sbarbati A, Crescimanno C, Osculati F (1999) The anatomy and functional role of the circumvallate papilla/von Ebner gland complex. Med Hypotheses 53:40–44
Sbarbati A, Merigo F, Bernardi P, Crescimanno C, Benati D, Osculati F (2002) Ganglion cells and topographically related nerves in the vallate papilla/von Ebner gland complex. J Histochem Cytochem 50:709–718
Li Z, Feng Z, Ye H (1995) Rabies viral antigen in human tongues and salivary glands. J Trop Med Hyg 98:330–332
Yohro T (1971) Nerve terminals and cellular junctions in young and adult mouse submandibular glands. J Anat 108:409–417
Chaudhari N, Roper SD (2010) The cell biology of taste. J Cell Biol 190:285–296
Kanazawa H (1993) Fine structure of the canine taste bud with special reference to gustatory cell functions. Arch Histol Cytol 56:533–548
Miura H, Kato H, Kusakabe Y, Ninomiya Y, Hino A (2005) Temporal changes in NCAM immunoreactivity during taste cell differentiation and cell lineage relationships in taste buds. Chem Senses 30:367–375
Evans HE (2013) Miller’s anatomy of the dog, 4th edn. Saunders, St. Louis, Missouri, pp 290–299
Hotta K, Motoi Y, Okutani A, Kaku Y, Noguchi A, Inoue S, Yamada A (2007) Role of GPI-anchored NCAM-120 in rabies virus infection. Microbes Infect 9:167–174
Thoulouze MI, Lafage M, Schachner M, Hartmann U, Cremer H, Lafon M (1998) The neural cell adhesion molecule is a receptor for rabies virus. J Virol 72:7181–7190
Hemachudha T, Ugolini G, Wacharapluesadee S, Sungkarat W, Shuangshoti S, Laothamatas J (2013) Human rabies: neuropathogenesis, diagnosis, and management. Lancet Neurol 12:498–513
Rupprecht CE, Hanlon CA, Hemachudha T (2002) Rabies re-examined. Lancet Infect Dis 2:327–343
Heckmann JG, Heckmann SM, Lang CJ, Hummel T (2003) Neurological aspects of taste disorders. Arch Neurol 60:667–671
Jackson AC (2013) Rabies, 3rd edn. Elsevier Saunders, Philadelphia, pp 179–213
Acknowledgements
The authors would like to acknowledge the invaluable help of staff at the Research Institute for Tropical Medicine (RITM), Department of Health, Philippines for tissue collection from dogs and the permission to use these samples in the current study. This work was supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (Kakenhi No. 26450410), and a grant for scientific research from the KITASATO University, Heiwa Nakajima Foundation, and AMED/JICA, SATREPS, Japan.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Ethics statement
The samples are dog’s heads which are clinical specimens routinely submitted for rabies diagnosis in the rabies laboratory of the Research Institute for Tropical Medicine (RITM) in the Philippines.
Additional information
Handling Editor: Marc H. V. Van Regenmortel.
Rights and permissions
About this article
Cite this article
Shiwa, N., Kimitsuki, K., Manalo, D.L. et al. A pathological study of the tongues of rabid dogs in the Philippines. Arch Virol 163, 1615–1621 (2018). https://doi.org/10.1007/s00705-018-3785-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00705-018-3785-y