Pet Rats Carry Two Zoonotic Viruses in a German Cluster of Human Exposure
Pet rats linked to human Seoul orthohantavirus infections in Germany also carried rat hepatitis E virus, placing two distinct zoonotic threats in the same animal population. In 3 of 13 pet rats studied, investigators identified rHEV RNA in liver tissue and confirmed prior SEOV infection in the same animals, a combination that raises the stakes for households, veterinarians, and primary care clinicians who may encounter febrile illness, hepatitis, or hantavirus exposure in pet owners.
The finding matters because pet rats are not just companion animals; they can serve as a bridge between captive breeding networks and human disease. Brown rats are natural reservoirs for a range of pathogens, and domesticated pet rats retain much of that infectious cargo. Here, the animals had already been tied to human SEOV infection in Germany, and the addition of rHEV broadens the diagnostic field when exposed patients present with nonspecific symptoms.
Liver Detection Pointed to Active Rat HEV Infection
RNA extracted from liver tissue underwent nested broad-spectrum RT-PCR designed to detect multiple HEV genotypes and rHEV. Sequencing identified rHEV RNA in 3 pet rats, and the result was confirmed with rHEV-specific real-time RT-PCR. Those 3 rats came from 3 different owners; 2 had been obtained from the same vendor, while the source of the third remained unknown. Their ORF1 sequences were nearly identical, with 99.15%–100% amino acid and nucleotide similarity across the 276-nt fragment analyzed.
Such close sequence identity points toward a single incursion event rather than repeated unrelated introductions. In practical terms, a shared source in the pet trade is more plausible than three independent infections arising in separate homes. The biology fits a transmission chain that began before the animals reached their owners, meaning the breeding or distribution network likely carried the pathogen forward.
Serology Suggested Wider Circulation Than the Sequenced Cases Alone
A multiplex serology approach detected rHEV-reactive antibodies in 12 of 13 pet rat blood samples, and 3 of those also reacted to HEV-3 antigen. Western blotting largely supported those findings: 11 of 12 multiplex-serology positive samples also tested positive for rHEV, and 10 of those 11 additionally reacted with HEV-3 antigen. All 3 RNA-positive rats had detectable rHEV-reactive antibodies.
The serologic pattern suggests more than a handful of isolated infections. High antibody prevalence in this small group is consistent with broader circulation in breeding facilities, even though the study did not include enough animals to define the true prevalence in the wider pet rat population. Assay differences may explain why multiplex serology and Western blot did not match perfectly, since each platform presents antigens differently and differs in sensitivity.
Sequence Relatedness Reached Beyond Germany
Full or near-full genomes from the 3 German pet rats were >99.7% identical to one another, and all 4 ORFs and encoded proteins were >99.2% identical. The closest published match was a wild brown rat sequence from Rotterdam, with full-sequence identity above 99.2% and each ORF above 98.3%. In the phylogeny, the pet rat sequences clustered with that Dutch wild-rat sequence.
This pattern does not prove the exact route of introduction, but it does suggest a shared ancestral virus circulating in brown rats and moving through connected rat populations. The most closely related German sequences outside the pet-rat cluster came from wild brown rats in Hamburg, while the only human rHEV sequence from Germany grouped separately among wild-rat sequences from Berlin. The genetic separation between the human sequence and the pet-rat cluster argues against a single nationwide rHEV lineage dominating all exposures.
Tissue Mapping Showed Hepatic Tropism for Rat HEV and Broad SEOV Spread
In situ hybridization using probes designed from the pet rat rHEV coding sequences produced a clear signal in the livers of the 3 rHEV-positive animals, specifically in hepatocytes. One rat also showed an oligofocal signal in the spleen, and another showed signal in the intestinal lumen. No signal appeared in the other tissues examined. The tissue pattern matches a hepatotropic virus and helps explain why rHEV remains a concern for hepatitis in exposed humans.
SEOV antigen, detected by nucleocapsid protein immunohistochemistry, was present in multiple organs of the co-infected rats, most prominently kidney and brain, and less often in spleen, intestine, liver, and lung. The organ distribution aligns with the known endothelial tropism of SEOV in natural and experimental rat infections. The overlap of a liver-focused hepevirus and a multi-organ hantavirus in the same animals creates a complicated zoonotic picture, even though tissue autolysis limited pathological assessment and prevented colocalization studies.
Public Health Signal for Households, Vendors, and Clinicians
The co-infection of pet rats with Seoul hantavirus and rat hepatitis E virus carries direct implications for zoonotic risk management. These animals were already linked to human SEOV infections in Germany, and the detection of rHEV adds another pathogen that can travel silently through breeding and trade networks. Owners who clean cages, handle bedding, or have close contact with pets may face exposure without recognizing the source.
Clinicians should keep pet rat exposure in mind when evaluating unexplained hepatitis, febrile syndromes, or suspected hantavirus illness. A history of rat ownership can help direct testing and infection-control advice. For public health teams, the near-identical rHEV sequences in the pet rats are especially important: they suggest a single introduction that may have spread through the pet supply chain, not an assortment of unrelated infections picked up after purchase.
The investigation had clear limits. Owners did not consent to blood sampling, so their rHEV serostatus remains unknown. Tissue damage from advanced autolysis reduced the ability to define pathology in detail, and the study could not assess whether both viruses occupied the same cells. Even so, the molecular and serologic data provide a strong warning: pet rats can carry more than one zoonotic virus at once, and the infection burden may extend beyond the pathogens already familiar to clinicians.