Spatial-Temporal Dynamics of Hepatitis E Virus Infection in Foxes (Vulpes vulpes) in Federal State of Brandenburg, Germany, 1993–2012

Abstract

Hepatitis E virus (HEV) is the main course for acute hepatitis in humans throughout the world. Human associated genotypes 1 and 2 as well as zoonotic genotypes 3 and 4 are grouped in the species Orthohepevirus A. In addition, a large variety of HEV-related viruses has been found in vertebrates including carnivores, rats, bats, and chickens, which were classified in species Orthohepevirus B-D. In 2015, partial genome sequences of a novel hepevirus were detected in feces of red foxes (Vulpes vulpes). However, no further information about virus circulation and the prevalence in foxes was available. We therefore assayed a unique panel of 880 transudates, which was collected from red foxes over 19 years (1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012) in Brandenburg, Germany, for HEV-related viral RNA and antibodies. Our results demonstrate a high antibody prevalence of HEV in red foxes, which oscillated annually between 40 and 100%. Molecular screening of the transudates revealed only a single RNA-positive sample, which was assigned to the carnivore species Orthohepevirus C based on the amplified partial sequence. These data indicate that the virus is circulating widely in the fox population and that foxes are carriers of this virus.

Identification of Hepatitis E Virus in the Feces of Red Foxes (Vulpes vulpes)

“…The phylogenetic analysis supports the aforementioned results. Based on the phylogeny ( Figure 1 ), our sample clustered with the cvHEV group, including the European common vole-hepeviruses rather than the novel HEV strain recently described from foxes in Germany (accession number: MN563782) [ 9 ]. Thus, suggesting that our sample contained cvHEV DNA originated from common voles ( Figure 1 ).…”

“…In contrast, a Syrian brown bear ( Ursus arctos syriacus ) in a German zoo was PCR positive for Rat-HEV without any disease symptoms, and serological evidence of Hepatitis E virus infection was confirmed in this animal, assumed a spillover infection of Rat-HEV from free-living Norway rats [ 3 ]. Recently, Eiden, et al [ 9 ] performed serological studies, where the high antibody prevalence of the virus demonstrated endemic HEV infections within a fox population in Germany, furthermore HEV genome sequence was reported in one case, also clustered to the Orthohepevirus C group. Since it is unknown if HEV associated clinical signs in foxes, it is assumed that they can be reservoir hosts for the virus [ 9 ].…”

“…Recently, Eiden, et al [ 9 ] performed serological studies, where the high antibody prevalence of the virus demonstrated endemic HEV infections within a fox population in Germany, furthermore HEV genome sequence was reported in one case, also clustered to the Orthohepevirus C group. Since it is unknown if HEV associated clinical signs in foxes, it is assumed that they can be reservoir hosts for the virus [ 9 ].…”

“…A similar finding was described from farmed American minks ( Neovison vison ) in Denmark [ 7 ] and represented as a new HEV variant. Further evidence of Carnivore-HEV was mentioned from red foxes ( Vulpes vulpes ) in the Netherlands [ 8 ] and recently in Germany [ 9 ]. All of these putative novel variants clustered with Rat-HEV, which was the exclusively known group within Orthohepevirus C before, but clustered in a separate phylogenetic branch that was distinct from other previously described Rat-HEV variants.…”

“…Since most of these novel variants were found in fecal samples of these animals, the dietary origin of the identified viruses was assumed, considering that these carnivores generally consume rodents [ 11 ]. However, according to studies conducted on red foxes in Germany, the high prevalence of HEV antibodies among this animal population indicated an endemic infection [ 9 ].…”