Detection of Systemic Canine Kobuvirus Infection in Peripheral Tissues and the Central Nervous System of a Fox Infected with Canine Distemper Virus

Abstract

Canine kobuvirus (CaKV) is a globally distributed pathogen of dogs and is predominantly associated with infection of the gastrointestinal tract. However, an etiological link to enteric disease has not been established since CaKV has been identified in both asymptomatic dogs and animals with diarrheic symptoms. In this study, an extraintestinal CaKV infection was detected by next-generation sequencing in a fox (Vulpes vulpes) in Germany concomitant with a canine distemper virus (canine morbillivirus; CDV) co-infection. Phylogenetic analysis of the complete coding region sequence showed that this strain was most closely related to a CaKV strain detected in a dog in the United Kingdom in 2008. The tissue and cellular tropism of CaKV was characterized by the detection of viral antigens and RNA. CaKV RNA was detected by in situ hybridization in different tissues, including epithelial cells of the stomach and ependymal cells in the brain. The use of a new RT-qPCR assay for CaKV confirmed the systemic distribution of CaKV with viral RNA also detected in the lymph nodes, bladder, trachea, and brain. The detection of a CDV infection in this fox suggests that immunosuppression should be further investigated as a contributing factor to the enhanced extraintestinal spread of CaKV.

Case report: Lympho-histiocytic meningoencephalitis with central nervous system vasculitis of unknown origin in three dogs

“…Pathogenetically, similar lesions can be triggered directly by an infectious agent or could be the result of immune-mediated pathogen-triggered mechanisms such as molecular mimicry or epitope-spreading [reviewed by Pederson ( 42 )]. Moreover, so far unknown pathogens not discovered by immunohistochemistry need to be considered, since several recent investigations using next generation sequencing have revealed new, so far unknown etiologies ( 43 , 44 ).…”

Evolutionary dynamics of canine kobuvirus in Vietnam and Thailand reveal the evidence of viral ability to evade host immunity

“…Furthermore, CaKoV has been detected in extraintestinal organs such as the liver, lungs, brain, and tonsils of puppies 32 . It was also found in various organs including stomach, brain, lungs, bladder, trachea, and intestinal lymph nodes of infected foxes 30 .…”

“…Following its initial detection in the USA, CaKoV has been identified in various countries, including Italy 19 , the United Kingdom 20 , China 21 – 24 , South Korea 25 , 26 , Japan 27 , Thailand 28 , Brazil 29 and Germany 30 . The pathological role of CaKoV in canine gastrointestinal diseases (GID) remains a topic of debate 2 , 21 , 27 , 31 .…”