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Aris Katzourakis

Dr Aris Katzourakis

Dr Aris Katzourakis

Research Fellow

Interests and expertise (Subject groups)

Grants awarded

Paleovirology, the genomic fossil record and consequences of viral gene flow

Scheme: University Research Fellowship

Organisation: University of Oxford

Dates: Oct 2015-Sep 2018

Value: £319,181.99

Summary: Animal genomes contain the remnants of ancient viruses, known as endogenous viral elements (EVEs). These EVEs form a genomic ‘fossil record’ that can be used to reconstruct viral evolution, a field of research known as paleovirology. My work revealed that all known viral types exist as EVEs, extending the scope of paleovirology from retroviruses to all viruses. By looking back into the distant past through this record, I aim to better understand the viruses that infect animals in the present day. The genomic fossil record has revealed that many viruses and their hosts have been engaged in evolutionary conflict that has spanned >100 million years. EVEs provide a crucial window into events that have long since passed. Some EVEs are stolen by the host and put to use as ‘domesticated’ viral genes to combat other incoming viruses. Conversely, viruses themselves can steal host genes and use them against their host. Thus, EVEs can be used to study the imprints of this ancient conflict, but can also be directly studied as active participants. The overarching aim of this project is to determine the role and nature of gene flow between viruses and their hosts, locked in an evolutionary arms race played out over millions of years. By understanding this evolutionary arms race, we will be better placed to design preventative and therapeutic strategies. As viruses insert into the genome, they can disrupt the functions of the cell and can lead to cancer. I have shown that mammalian body size limits the number of endogenous retroviruses that an animal can carry, with larger organisms having fewer viruses. I proposed that this is because the risk that integrated viruses could lead to cancer should scale with the number of cells in an organism. I will determine whether the tumorigenic risk of viral integration has led to the evolution of mechanisms that control viral activity. This work could provide insights into cancer susceptibility.

The Evolutionary Biology of Retroviruses

Scheme: University Research Fellowship

Organisation: University of Oxford

Dates: Oct 2010-Sep 2015

Value: £554,188.24

Summary: Retroviruses are a group of viruses that infect the genomes of their hosts, and are responsible for a wide range of diseases, most notably HIV/AIDS. In common with other RNA viruses, retroviral evolution occurs very rapidly. This property has greatly facilitated studies into the recent evolutionary biology of retroviruses, such as dating the origin of the viruses responsible for the HIV pandemic. The rapid rate of evolution of retroviruses has at the same time obscured their more distant history due to the erosion of the evolutionary signal in viral genomes of events that have occurred millions of years ago. Retroviruses are unusual among mico-organisms in possessing a rich ‘fossil record’, somewhat analogous to the palaeontological fossil record, resulting from the integration of the viral genome into the DNA of the host. Occasionally, this integration occurs in the reproductive tissue of the host, and the virus is transmitted to the offspring. These inherited viruses are known as endogenous retroviruses (ERVs), and can yield unique information about the evolution of retroviruses that could not be obtained using contemporary sequence data. Once in the genome, ERVs can copy themselves to other locations; ~5% of the human genome is derived from ERVs, far more than codes for proteins (around 1%). My research combines evolutionary biology, mathematical modelling, in vitro experimental tests and sequencing, in order to answer fundamental questions regarding retroviral biology. I aim to understand both the evolutionary dynamics of ERVs within genomes, as well as the macroevolutionary processes that govern retroviral evolution in general. Answering these questions will provide a valuable tool for predicting the outcome of infection, and identifying potential sources of future emerging infections. Furthermore, an understanding of the role of retroviruses in shaping the host immune response could help guide future treatments to retroviral infection.

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