Tropism, pathology, and transmission of equine parvovirus-hepatitis

Abstract

Equine parvovirus-hepatitis (EqPV-H) has recently been associated with cases of Theiler's disease, a form of fulminant hepatic necrosis in horses. To assess whether EqPV-H is the cause of Theiler's disease, we first demonstrated hepatotropism by PCR on tissues from acutely infected horses. We then experimentally inoculated horses with EqPV-H and 8 of 10 horses developed hepatitis. One horse showed clinical signs of liver failure. The onset of hepatitis was temporally associated with seroconversion and a decline in viremia. Liver histology and in situ hybridization showed lymphocytic infiltrates and necrotic EqPV-H-infected hepatocytes. We next investigated potential modes of transmission. Iatrogenic transmission via allogeneic stem cell therapy for orthopedic injuries was previously suggested in a case series of Theiler's disease, and was demonstrated here for the first time. Vertical transmission and mechanical vectoring by horse fly bites could not be demonstrated in this study, potentially due to limited sample size. We found EqPV-H shedding in oral and nasal secretions, and in feces. Importantly, we could demonstrate EqPV-H transmission via oral inoculation with viremic serum. Together, our findings provide additional information that EqPV-H is the likely cause of Theiler's disease and that transmission of EqPV-H occurs via both iatrogenic and natural routes. Materials and methods AnimalsHorses were 2-27 years old, 10 mares and 7 geldings, and 4 Warmbloods, 3 Thoroughbred crosses, 2 each

Equine parvovirus hepatitis

“…In all horses, peak viraemia was observed approximately 5 weeks after infection, with the highest viral load detected in the serum and liver [21]. Furthermore, viral DNA was also present in various organs and body fluids, such as synovial fluid, CSF, heart, kidney, colon, jejunum, synovium, salivary gland, bone marrow, lymph node, spleen, spinal cord, and lung [21]. The virus persisted at low levels in the majority of tested body fluids and tissues for at least 15 weeks after infection [21].…”

“…EqPV-H transmission by horse flies could, however, not be demonstrated in a recent study and was hypothesised to require a large number of bites [21]. Intermittent shedding of EqPV-H via the nasal, oral, and faecal routes was recently reported for experimentally infected horses [21]. Although shedding events were centred around the time of peak viraemia, it could continue for 10 weeks after infection [21].…”

Circovirus in Blood of a Febrile Horse with Hepatitis

“…Real time PCR tests performed by Cornell University Animal Health Diagnostic Center reported negative results for the flavivirus equine hepacivirus and positive results for equine parvovirus (EqPV-H) with Ct values of 32.36. EqPV-H, a frequent equine infection [34,35], has been associated with and shown to induce hepatitis following inoculation although many EqPV-H infections are also asymptomatic [36][37][38].…”

Equine pegiviruses cause persistent infection of bone marrow and are not associated with hepatitis

“…Since EPgV-2 infections have also not been identified in cases of equine serum hepatitis subsequent to the initial outbreak, these data further substantiates the lack of association between TDAV and liver disease. Rather, the novel equine parvovirus, EqPV-H, was identified in many investigated cases of acute serum hepatitis, as well as other cases of acute liver disease in horses [ 36 – 39 ]. Interestingly, EqPV-H was retrospectively also identified in the original EPgV-2/TDAV-contaminated inoculum [ 36 ].…”

“…Since pegiviruses generally are not associated with clinical disease, it was a surprise when TDAV was found in an outbreak of acute serum hepatitis [13]. No additional links between EPgV-2 and clinical cases of equine liver disease have been reported; instead a recently discovered parvovirus (EqPV-H) appears responsible for a number of Theiler's disease cases in horses [36][37][38][39][40][41]. So far, however, the possible link between equine pegiviruses and hepatitis has not been formally examined.…”