Retroviruses have a peculiar lifecycle, which involves copying themselves into the genome of the host cell they’re infecting. As a consequence, they can become integrated into the germ line of the host species. This is actually a very common process and all vertebrate genomes contain multiple groups of endogenous retroviruses (ERVS).
In some genomes, like the human and mouse, there is more retroviral material than protein coding sequence. The retroviruses aren’t generally functional due to the accumulation of mutations over time, so we refer to them as retroviral fossils. Whether they exist primarily as genetic parasites, should be considered as commensals or are advantageous to the host, is a fundamental question of genome evolution.
Recent work across many species suggests endogenous retroviruses have a significant effect on the RNA level regulation of gene expression in their hosts. This makes them a significant source of genetic variation in some species.
In some more recent retroviral integrands including those in cats and koalas, it can be very hard to distinguish the endogenous versions from their infectious counterparts. The infectious and inherited forms of the virus can and do swap gene segments and influence disease pathogenesis in complex ways.
Our research and its impact
Here in the One Virology Research Group, we’ve developed bio-informatics methods for Illumina and nanopore data for identifying and classifying ERVS in genomic information, as well as mapping their expression in transcriptomics data sets.
Along with more conventional qPCR and population level epidemiology studies, we’ve been applying these methods to a variety of species and disease syndromes. We’ve characterised ERVs in dogs, horses, non-human primates, cats, chickens, pigs, elephants and rodents.
One major research focus is koala retrovirus (KoRV), which is transitioning into an ERV and having a significant impact on its host’s genetics and pathology. We’re working with teams at the University of Queensland and the University of Adelaide with funding from the QLD department of the environment and heritage, influencing disease and population management programmes for this threatened species. Our recent work with Long Leat safari park and the University of Melbourne has identified defective versions of the virus in populations with low viral loads. These variants may be inhibiting the infectious virus. Other work in collaboration with the Leibniz Institute for zoo and wildlife research has demonstrated that KoRV is definitely responsible for the very high rates of cancer in some koala populations.
Other work (with funding from Conicyt Chile) will extend the nanopore enrichment used to identify KoRV loci (both insertion site and virus sequence) into Endangered South American Felids infected with Feline leukaemia virus (a spill over event from domestic cats). This work will allow us to develop the technology closer to field use and examine which FeLV variants are entering the endangered felids (a critical question for vaccine options)
A further current research stream is focused on the expression of human retroviruses of the HERV-W group and their role in the underlying pathogenesis of multiple sclerosis. This project with Dr Bruno Gran at Nottingham University Hospitals NHS trust has current funding from Roche UK to examine viral loads and antiviral responses to Epstein Barr Virus and HERV-W in MS patients starting treatment with Ocrelizumab (which depletes B cells). Our end aim is to work out how the different risk factors for the disease work together in triggering MS. If we can successfully achieve this, it will make preventing future cases of MS a real possibility.
Find out more about our koala retrovirus project