Evasion of innate immunity by vaccinia virus

Poxviruses replicate in the cell cytoplasm and have large dsDNA genomes. The most infamous poxvirus is variola virus, the cause of smallpox, a disease eradicated by vaccination with vaccinia virus (VACV), a related orthopoxvirus. Monkeypox virus is another orthopoxvirus that has caused a worldwide epidemic in 2022-3 with ~ 90,000 confirmed cases and ~150 deaths. These viruses express about 200 proteins with those required for virus replication encoded predominantly near the centre of the genome, whilst genes towards either end encode factors dispensable for virus replication, but which function to suppress the innate immune response to infection. This talk will describe host factors that restrict poxviruses and viral evasion strategies. The talk will also consider how gene loss has contributed to the evolution of variola virus in humans and might do so for monkeypox virus.

Geoffrey L. Smith obtained his PhD (1981) for work with influenza virus at NIMR, London. Then as a postdoc with Bernard Moss at NIH, USA (1981-4) he developed vaccinia virus (the smallpox vaccine) as an expression vector and established the principle of using genetically engineered viruses as live vaccines. He continued studying poxviruses after returning to UK at Cambridge (1985-9), Oxford (1989-2000), Imperial College London (2000-11), Cambridge (2011-22) and again at Oxford from 2023. His research group studies the interactions of poxviruses with the host cell and immune system.

Previously, he was President of the International Union of Microbiological Societies and Chair of the WHO Advisory Committee for Variola Virus Research, the Scientific Advisory Board of the Centre for Structural and Systems Biology Hamburg, the Royal Society Committee for Scientific Aspects of International Security, and the Scientific Advisory Board of the Friedrich-Loeffler Institute (German Ministry for Food and Agriculture). He was a member of the University Research Grants Council Hong Kong, and currently is Chair of the Scientific Advisory Board of the Pirbright Institute, UK. He is a member of the Royal Society, UK and Leopoldina – the German National Academy of Sciences.