EVAg

Presented by E A Gould

Two internationally prominent UK arbovirologists, Richard Elliott and Tamara Gritsun, who were both very close friends of many EVA members have independently lost their fight against cancer.  Their departure from this world is terribly sad and it is also a major loss to the arbovirus world.  Their contrasting scientific styles, innovative approaches and unique contributions to arbovirology were extraordinary.  They will both be missed.

Professor Richard Elliott (1954-2015)

 Richard Elliotts’ career as a virologist began with his postgraduate studies for a PhD in the Institute of Virology, Oxford under the supervision of the late Dr David Kelly. He then moved to the Mount Sinai Medical School in New York to work as a post-doctoral scientist under Professor Peter Pelese and followed this by moving back to the UK in 1981 and joining the MRC Virology Unit in Glasgow. He subsequently moved to the University Department of Virology in Glasgow as a Senior MRC Fellow in 1986 and was appointed Professor of Molecular Pathogenesis in 1995 and joint Head in the Division of Virology in 1998.  In 2005 he was appointed Professor of Virology at the University of St Andrews but more recently returned to Glasgow to take an appointment as holder of the Bill Jarrett Chair of Infectious Diseases.

As a researcher, Richard was best known for his studies on bunyaviruses and hantaviruses. However, he was also devoted to teaching undergraduates and supervising postgraduate students for their doctorates. He was incredibly well-liked 

One of Richard’s many gifts reflected his broad scientific background which enabled him to develop and interpret scientific research and discoveries at both the biological and molecular level. During his career his name became synonymous with fundamental research on bunyaviruses. For example, he discovered many of the important aspects of viral virulence, gene regulation, virion assembly, the viral replication cycle, the underlying mechanisms with which these viruses foil the immune responses of the hosts that they infect and development of attenuated viruses as potential vaccines.  Richard was at the forefront of many technological developments. Perhaps his most extraordinary research success was to develop the first method for rescuing a negative-sense RNA virus, in this case, Bunyamwera virus from cloned cDNA. This unrivalled and extremely challenging achievement subsequently laid the first stone for many equivalent accomplishments for other viruses including influenza virus! Richard continued to exploit the flexibility of reverse genetics by applying his newly developed methods to a variety of other bunayviruses including Rift Valley fever virus, Uukuniemi virus and even hantaviruses.by students and his peers and was also a popular choice as a plenary speaker at both national and international congresses.

Richard’s knowledge and broad experience in virology for so many years also made him an ideal contributor to viral taxonomy through ICTV and as an editor in chief for the Journal of General Virology.  He was a totally dedicated virologist, loved by all who worked with him and will be remembered not only for his brilliant contribution to arbovirology but also as a kind, considerate, dedicated scientist and teacher who has given so much to the world. 

Dr Tamara Segeevna Gritsun (1956-2015)

Tamara Gritsun graduated with an honour’s degree from Moscow State University in 1980. Her career as a virologist then began with postgraduate studies in the Medical Academy of Sciences Institute of Poliomyelitis and Viral Encephalitides, Moscow, Russia.  She obtained her PhD in 1987, focusing primarily on biochemical studies of West Nile virus and tick-borne encephalitis virus (TBEV), the latter becoming her speciality for the remainder of her scientific career.  In the late 1980s

Her studies on the non-structural NS1 protein of TBEV were years ahead of western scientists when she described oligomeric molecules, one of which was hexameric (with a doughnut-like appearance) and membrane associated. This was subsequently –“re-discovered” by western scientists years later!  

In 1990 Tamara moved to Oxford where she worked in Dr Gould’s research team, having to learn to speak English whilst teaching and supervising D Phil and other students, many of whom have since progressed to senior career positions.

Within two years of commencing research in Oxford, Tamara embarked on a project that nearly everyone in the lab thought was bound to fail. The objective was to develop an infectious clone of TBEV using high fidelity reverse transcription to synthesise full-length genomic cDNA which was then in vitro transcribed to produce full-length RNA which I inoculated directly into newborn mice.  For the first year or more many tears were shed as test after test failed. However, with perseverance and using her strong organic chemistry background, Tamara achieved her first goal, ie to prodice the full length genome in two halves which were ligated together. This led to the first infectious virus being recovered directly using RT PCR methodology. Within another year full-length genomes were being synthesised by RT PCR and the in vitro transcribed RNA proved to be infectious.  This technology reduced the time to produce an infectious clone from years to weeks.

Tamara was also determined to demonstrate that chronic tick-borne encephalitis was a real disease in Russia. Using molecular methods she demonstrated that the virus persistence in brains of healthy animals and humans is responsible for a range of slowly progressive neurological sequelae.

Her research on the evolution of structure and function of the untranslated regions (UTRs) of viral RNA, was innovative and has wide implications in our understanding of viral replication mechanisms in association with virus virulence, evolution, innate immunity. It also also has practical applications for the development of live attenuated vaccines and antiviral therapeutics.

Tamara developed her own unique methods of comparing RNA sequences that were disparate (particularly amongst UTR sequences).  This led to the discovery of “ancestral building blocks” that were in fact repeated sequence elements. Her manual sequence alignment technique then demonstrated very clearly the evolutionary process of insertion and deletion which when associated  with polymerase infidelity illustrated the simple but effective mechanism by which evolution could progress rapidly, ultimately being refined by conventional single base substitutions.

Tamara also applied her imaginative mind to understanding the role of ticks in TBEV pathogenesis. A paper describing the results of this work is currently being completed and will be one of at least two papers that will appear as a tribute to her wonderful contribution to arbovirology.

Finally, during the past two years Tamara was developing a novel approach to understanding the molecular basis of viral neuropathogenesis.  This project tested her molecular and biocomputational skills to the limit but the result has been a tremendous success.  We tried to complete the manuscript before Tamara lost her fight with cancer.  Unfortunately, we were too late but we are optimistic that once published this paper will leave a lasting legacy of her amazing contribution to arbovirology.

It is a fitting tribute to Tamara that people from all over the world visited her during her illness and many more sent her messages of endearment. Her memory will live on through her science!