Investigation of intranuclear inclusion bodies in the hepatocytes of the koala and potential association with herpesvirus infection

Abstract

Hepatocellular inclusion bodies are frequently observed in koalas during postmortem examinations, but their cause is unknown. Suspected origins include viral infection, glycogen or protein accumulation, or cytoplasmic invaginations. Koalas are susceptible to two gammaherpesviruses, Phascolarctid herpesvirus-1 (PhaHV-1) and Phascolarctid herpesvirus-2 (PhaHV-2). The clinical relevance of these viruses remains unclear. This study aimed to: (1) characterise the epidemiology of hepatocellular intranuclear inclusions of koalas; and determine whether these inclusions are associated with (2) other liver pathology or (3) PhaHV-1 or PhaHV-2 infection. A retrospective review and prospective, opportunistic, sample collection were undertaken. Epidemiologic data was investigated and liver histopathology analysed using a developed grading system. Liver and spleen samples from 34 koalas were tested by qPCR for PhaHV-1 and PhaHV-2. Koalas from the state of Queensland had a higher prevalence of inclusions than those from NSW, but no differences were found by age, sex, or captive/wild status. Inclusions were more common in koalas with chlamydiosis (OR 4.27) or neoplasia (OR 4.85) than in trauma cases. Affected koalas also showed increased hepatocellular anisokaryosis (OR 29.79). No association was found between inclusion presence and PhaHV-1 or PhaHV-2 infection. These findings suggest PhaHV-1 and PhaHV-2 are both unlikely to directly cause the inclusion bodies. Instead, the association with chronic disease and anisokaryosis points to increased hepatic metabolic demand and turnover as a potential contributing factor.