Poxviruses

Event Date: 
Wednesday, April 30, 2014 - 19:00 - 20:00
Institution: 
Marie Bashir Institute for Infectious Disease and Biosecurity, Charles Perkins Centre, School of Biological Sciences and Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia.
Title: 

The Greatest Experiment in Evolution: Viral Biocontrol of Rabbits

Abstract: 

The wild European rabbit (Oryctolagus cuniculus) was successfully introduced into Australia in 1859.  By the early 1900s rabbits had crossed the borders of all mainland states spreading at a rate of about 70 km a year, the fastest of any colonising mammal.  By the 1950s there may have been more than one billion rabbits in Australia.  The introduction of the rabbit has irrevocably changed the Australian landscape, significantly affecting both native flora and fauna.  Rabbits have therefore been vigorously targeted through the deliberate introduction of two viral control agents: Myxoma virus (MYXV) was successfully released in Australia in the 1950s, while Rabbit Haemorrhagic Disease Virus (RHDV) escaped from quarantine field trials in 1995.
 
Through the application of genome-scale phylogenetic methods I will describe the patterns, processes and outcomes of these unique and grand-scale experiments in evolution.  In particular, I will show how viral virulence has evolved in both cases (the example of MYXV in European rabbit is the canonical study of the evolution of virulence), and how phylogenetic methods provide a valuable insight into the genomic determinants of virulence evolution.  In addition, phylogenetic analysis of the spread of both MYXV and RHDV in the Australian environment provides key information on the rates, patterns and dynamics of pathogen evolution in a naïve environment, and represents a powerful analogy to cases of disease emergence following cross-species virus transmission to a novel host.
 
I will close by discussing the possible evolutionary consequences of the next grand viral biocontrol experiment planned for Australia: the release of Koi herpesvirus (KHV) to control the common carp that was also introduced to Australia in the 19th Century.

Dear JAMSters,

With the Holiday season well underway I wanted to wish you all lasting health and happiness for the coming new year and thank you for making JAMS such a success this year.

Next year promises to be even better and will start off with a great lineup for our January 25th meeting:

Event Date: 
Wednesday, January 25, 2012 - 18:00 - 18:15
Institution: 
University of Sydney
Title: 

Vaccinia Virus BTB-Kelch Proteins and the Ubiquitin-Proteasome System during poxvirus infection.

Abstract: 

Vaccinia virus (VACV)—the live-virus vaccine used to eradicate smallpox (Variola virus)—encodes three BTB-Kelch protein (BBK) orthologues, a family of cellular proteins that have demonstrated roles in the Ubiquitin-Proteasome System (UPS). The UPS is the common mechanism by which specific proteins are degraded at specific times inside the host cell. Substrate proteins are multiply-ligated with ubiquitin and are thus flagged for degradation by the 26S Proteasome. If an invading virus were to commandeer such a system it may be rewarded with a unique and powerful solution to avoid the intrinsic cellular defences. BBKs function as UPS substrate adaptors, acting as a link between the ubiquitination machinery and the ubiquitin-ligated substrates themselves.

By encoding BBKs VACV can hijack the UPS and selectively degrade a wide range of host proteins to its advantage; preventing the establishment of an antiviral immune response, transforming the cell into a virus-production factory or enhancing viral spread. Manipulation of the UPS is a phenomena known to play a role in mediating infection in many other viral contexts. The identification of VACV BBK substrates may highlight new mechanisms by which VACV and other viruses overcome the intrinsic cellular defences to mediate infection.

We have previously shown, using fluorescently tagged BBKs, partial colocalisation with the ubiquitinylation machinery, indicating that these proteins act via a common UPS-based mechanism. These results are consistent with partial redundancy observed in BBK mutants and the obstructive effect of UPS inhibitors on poxvirus replication. We are now attempting to further elucidate any potential interactions and dissect the global implications of poxviral interactions with the UPS.

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