CLINICAL SIGNS, DIAGNOSIS AND TREATMENT
Evidence in support of a pathogenic role of KoRV is growing, but the mechanisms and extent are still unclear. If, as has been proposed, KoRV does induce or predispose to chlamydial infertility and death, immunosuppressive or opportunistic infectious diseases, joey loss, blood and bone marrow disorders (myelodysplasia) or neoplasms (e.g.
lymphoma and leukaemia, mesothelial and craniofacial tumours), diagnosis of KoRV infection would have clinical implications that might range from quarantine, breeding or population management, to indication for antiviral therapy or vaccination, to prognosis for case management.Diagnosis of infection is based on PCR of DNA from blood, faeces or tissues to detect provirus. In the case of exogenous viruses it should be borne in mind that tissue tropism has not been defined and the tissue type sampled is predominantly chosen on the basis of access. Detection of expressed virus is by reverse transcription PCR of RNA extracted from plasma. For generic detection or quantification of all KoRV subtypes, pol gene primers can be used, but detection of specific subtypes requires the use of specific env gene primers. For screening of all known and unknown KoRV subtypes, deep-sequencing of the env gene would be the appropriate approach.
Effective application of antiviral therapy will likely require a greater knowledge base than simply evidence of causation. Kinney and Pye (2016) review some of these issues, including the specificity of antiviral drugs to pathogenic pathways, which have not yet been identified for KoRV (Lifson 2014), as well as the precedents for rapid metabolism of some therapeutic drugs by koalas (Griffith et al. 2010; Kimble et al. 2014). Published work on vaccine development is preliminary. Neutralising antibodies to KoRV have been generated in laboratory species (Fiebig et al. 2015a), but studies are equivocal on whether koalas endogenously infected by KoRV are able to generate antibodies against KoRV antigens (Fiebig et al. 2015b; Waugh et al. 2016).
Given the complexity around the role of KoRV in disease, research is urgently needed to inform to what degree clinical decisions should be based on detection of KoRV by PCR. The field is moving rapidly, however, and accumulation of clinical, infection and immunological data is likely to assist the development and evaluation of diagnostic or immunological tests on which clinical or population management decisions might be based.