CURRICULUM VITAE PETER SIMMONDS, BM, PhD, FRCPath, FRS(E) Date 18th December, 2015 Contact information Nuffield Department of Experimental Medicine University of Oxford Peter Medawar Building South Parks Road Oxford, OX1 3PS Tel. Email. 01865 281 233 Peter.Simmonds@ox.ac.uk Qualifications Batchelor of Medicine (BM), University of Southampton, July, 1982 General Medical Council Registration (GMC no. 2571014) - August, 1993 PhD, University of Edinburgh, July, 1988 MRCPath in Virology (by Exam), July, 1994 Current Appointments Professor of Virology, University of Oxford (since April, 2016) Research Interests and Career highlights My main current research programme is in the investigation of the evolutionary and functional basis for the pervasive suppression of CpG and UpA dinucleotides in RNA viruses. Modelling evidence I obtained for selection against them in cytoplasmically-expressed RNA sequences demanded functional investigations. The discovery that viruses with high frequencies of CpG/UpA are recognised and suppressed by as yet uncharacterised intrinsic defence mechanisms suddenly opens exciting, new areas of enquiry into innate immunity in mammalian cells. Conversely, accelerated replication of viruses with suppressed frequencies confronts us with a seeming evolutionary paradox which we will investigate through experimental investigations of relationships between disease processes and transmission dynamics. Other ongoing and recent research has been focussed on the characterisation of RNA secondary structure in viruses, and its effect on virus evolution. Discovery of large scale RNA structure in many families of positive-stranded RNA viruses followed the development of large-scale bioinformatic methods to quantify and characterise RNA secondary structure formation in viral genomes. The association of genome-scale organised RNA structure (GORS) with host persistence, and the finding that their genomes are structured in a fundamentally different way from those causing acute infections has been the subject of ongoing investigations of the nature of virus interactions with host cell defences modulated by doublestranded RNA, the physical structure of the predicted RNA structures and the influence of RNA structure as a sequence constraint on the evolution of persistent viruses. This area of research has also initiated a series of functional studies of the role of RNA secondary structure elements in the replication of HCV (Professor David Evans, University of Warwick), caliciviruses (Dr Ian Goodfellow, Imperial College, London) and hepatitis A virus (Professor S. Lemon, University of Texas Medical Branch). A second area of research focuses on the molecular epidemiology, evolution and emergence of a wide range of human pathogenic viruses. This includes aetiological investigations of the role of known and recently discovered viruses in respiratory, enteric and neurological disease. I am closely involved in an active ongoing programme of research in clinical virology in its broadest sense with investigations ranging from basic science molecular epidemiology, evolutionary and pathogenicity studies through to investigations of the impact and newly discovered and emerging viruses in human health, and the development of diagnostics for patient screening and monitoring. Collectively, these investigations fit into a broader theme of research work in the nature of evolutionary process in RNA viruses, how it differs from that of their mammalian hosts, how this and recombination shapes their molecular epidemiology and clinical manifestations. PUBLICATIONS Publications 446 authored papers listed on Medline 28 book chapters Citations Google Scholar h-index = 95 31,498 citations i10-index = 321 Web of Science h-index = 80 25,196 citations Recent published papers 2015 Boros, A., P. Pankovics, P. Simmonds, E. Pollak, R. Matics, T. G. Phan, E. Delwart, and G. Reuter. 2015. Genome analysis of a novel, highly divergent picornavirus from common kestrel (Falco tinnunculus): The first non-enteroviral picornavirus with type-I-like IRES. Infect. Genet. Evol. 32:425431. Gaunt, E., H. Harvala, R. Osterback, S. Vattipally, E. Thomson, M. Waris, and P. Simmonds. 2015. Genetic characterisation of Coxsackievirus A6 variants associated with atypical hand, foot and mouth disease; a potential role of recombination in emergence and pathogenicity. J. Gen. Virol. 96:10671079 Kapoor, A., A. Kumar, P. Simmonds, N. Bhuva, C. L. Singh, B. Lee, A. A. Sall, Z. Jin, S. S. Morse, B. Shaz, P. D. Burbelo, and W. I. Lipkin. 2015. Virome Analysis of Transfusion Recipients Reveals a Novel Human Virus That Shares Genomic Features with Hepaciviruses and Pegiviruses. MBio. 6:e01466-15 Matthews, P. C., C. P. Sharp, A. Malik, W. F. Gregory, E. Adland, P. Jooste, P. J. Goulder, P. Simmonds, and P. Klenerman. 2015. Human Parvovirus 4 Infection among Mothers and Children in South Africa. Emerg. Infect. Dis. 21:713-715. Scheel, T. K., P. Simmonds, and A. Kapoor. 2015. Surveying the global virome: Identification and characterization of HCV-related animal hepaciviruses. Antiviral Res. 115C:83-93. Simmonds, P., F. Tulloch, D. J. Evans, and M. D. Ryan. 2015. Attenuation of dengue (and other RNA viruses) with codon pair recoding can be explained by increased CpG/UpA dinucleotide frequencies. 2 Proc. Natl. Acad. Sci. U. S. A. 112:E3633-E3634 Simmonds, P. 2015. Methods for virus classification and the challenge of incorporating metagenomic sequence data. J. Gen. Virol. 96:1193-1206 Smith, D. B., S. Ijaz, R. Tedder, B. Hogema, H. Zaaijer, J. Izopet, A. Bradley-Stewart, R. Gunson, H. Harvala, I. Kokki, and P. Simmonds. 2015. Variability and pathogenicity of Hepatitis E virus genotype 3 variants. J. Gen. Virol.10 2014 Atkinson, N. J., D. J. Evans, and P. Simmonds. 2014. The influence of CpG and UpA dinucleotide frequencies on RNA virus replication and characterisation of the innate cellular pathways underlying virus attenuation and enhanced replication. Nucleic Acids Res. 42:4527-4545 Cabrerizo, M., G. Trallero, and P. Simmonds. 2014. Recombination and evolutionary dynamics of human echovirus 6. J Med Virol. 86:857-864 Firth, C., M. Bhat, M. A. Firth, S. H. Williams, M. J. Frye, P. Simmonds, J. M. Conte, J. Ng, J. Garcia, N. P. Bhuva, B. Lee, X. Che, P. L. Quan, and W. I. Lipkin. 2014. Detection of Zoonotic Pathogens and Characterization of Novel Viruses Carried by Commensal Rattus norvegicus in New York City. MBio. 5:e01933-14. Harvala, H., D. Smith, K. Salvatierra, R. Gunson, B. von Wissmann, A. Reynolds, C. Frew, A. MacLean, A. Hunt, D. Yirrell, P. Simmonds, J. McMenamin, and K. Templeton. 2014. Burden of influenza B virus infections in Scotland in 2012/13 and epidemiological investigations between 2000 and 2012. Euro. Surveill. 19:20903. Harvala, H., J. Calvert, D. Van Nguyen, L. Clasper, N. Gadsby, P. Molyneaux, K. Templeton, L. C. McWilliams, and P. Simmonds. 2014. Comparison of diagnostic clinical samples and environmental sampling for enterovirus and parechovirus surveillance in Scotland, 2010 to 2012. Euro. Surveill. 19:20772. Harvala, H., D. Van Nguyen, C. McIntyre, S. Ahuka-Mundeke, N. E. Mpoudi, E. Delaporte, M. Peeters, and P. Simmonds. 2014. Co-circulation of enteroviruses between apes and humans. J Gen Virol. 95:403407 Harvala, H., V. Wong, P. Simmonds, I. Johannessen, and S. Ramalingam. 2014. Acute viral hepatitis Should the current screening strategy be modified? J Clin Virol. 59:18410-187 Harvala, H., M. Griffiths, T. Solomon, and P. Simmonds. 2014. Distinct systemic and central nervous system disease patterns in enterovirus and parechovirus infected children. J Infect. 69:69-74 Iles, J. C., J. Raghwani, G. L. Harrison, J. Pepin, C. F. Djoko, U. Tamoufe, M. Lebreton, B. S. Schneider, J. N. Fair, F. M. Tshala, P. K. Kayembe, J. J. Muyembe, S. Edidi-Basepeo, N. D. Wolfe, P. Simmonds, P. Klenerman, and O. G. Pybus. 2014. Phylogeography and epidemic history of hepatitis C virus genotype 4 in Africa. Virology. 464-465: 233-243 Lyons, S., A. Kapoor, B. S. Schneider, N. D. Wolfe, G. Culshaw, B. Corcoran, A. E. Durham, F. Burden, B. C. McGorum, and P. Simmonds. 2014. Viraemic frequencies and seroprevalence of non-primate hepacivirus and equine pegiviruses in horses and other mammalian species. J Gen Virol. 95: 1701-1711. 3 . Nguyen, D. V., A. H. Pham, C. V. Nguyen, H. T. Ngo, J. Carrique-Mas, H. B. Vo, J. Campbell, S. Baker, J. Farrar, M. E. Woolhouse, J. E. Bryant, and P. Simmonds. 2014. Prevalence, genetic diversity and recombination of species G enteroviruses infecting pigs in Vietnam. J Gen Virol. 95:549-556 Nishiyama, S., B. M. Dutia, J. P. Stewart, A. L. Meredith, D. J. Shaw, P. Simmonds, and C. P. Sharp. 2014. The identification of novel anelloviruses with broad diversity in UK rodents. J Gen Virol. 95: 1544-1553. Servant-Delmas, A., S. Laperche, F. Lionnet, C. Sharp, P. Simmonds, and J. J. Lefrere. 2014. Human parvovirus 4 infection in low- and high-risk French individuals. Transfusion. 54:744-745 Siebrasse, E. A., N. L. Nguyen, C. Smith, P. Simmonds, and D. Wang. 2014. Immunohistochemical detection of KI polyomavirus in lung and spleen. Virology. 468-470 :178-184 Simmonds, P. 2014. Methods for virus classification and the challenge of incorporating metagenomic sequence data. J. Gen. Virol. Dec 11 [Epub ahead of print]. Sinclair, C., E. Gaunt, P. Simmonds, D. Broomfield, N. Nwafor, L. Wellington, K. Templeton, L. Willocks, O. Schofield, and H. Harvala. 2014. Atypical hand, foot, and mouth disease associated with coxsackievirus A6 infection, Edinburgh, United Kingdom, January to February 2014. Euro. Surveill. 19:20745 Smith, D. B., P. Simmonds, and J. E. Bell. 2014. Brain viral burden, neuroinflammation and neurodegeneration in HAART-treated HIV positive injecting drug users. J Neurovirol. 20:28-38 Smith, D. B., J. Bukh, C. Kuiken, A. S. Muerhoff, C. M. Rice, J. T. Stapleton, and P. Simmonds. 2014. Expanded classification of hepatitis C Virus into 7 genotypes and 67 Subtypes: updated criteria and assignment web resource. Hepatology. 59:318-327 Smith, D. B. and P. Simmonds. 2014. Hepatitis E virus and fulminant hepatitis-a virus or host-specific pathology? Liver Int.10 Smith, D. B., P. Simmonds, S. Jameel, S. U. Emerson, T. J. Harrison, X. J. Meng, H. Okamoto, W. H. Van der Poel, and M. A. Purdy. 2014. Consensus proposals for the classification of the family Hepeviridae. J. Gen. Virol. 95: 2223-2232. Tulloch, F., N. J. Atkinson, D. J. Evans, M. D. Ryan, and P. Simmonds. 2014. RNA virus attenuation by codon pair deoptimisation is an artefact of increases in CpG/UpA dinucleotide frequencies. eLife 3: e04531. Van Nguyen, D., H. Harvala, E. M. Ngole, E. Delaporte, M. E. Woolhouse, M. Peeters, and P. Simmonds. 2014. High rates of infection with novel enterovirus variants in wild populations of mandrills and other Old World Monkey species. J Virol. 88:5967-5976 Witteveldt, J., R. J. Blundell, J. Maarleveldt, N. McFadden, D. J. Evans, and P. Simmonds. 2014. The influence of viral RNA secondary structure on interactions with innate host cell defences. Nucleic Acids Res. 42:3314-3329 4