P Simmonds

The University of Edinburgh, Edinburgh, Scotland, United Kingdom

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Publications (424)3165.44 Total impact

  • European Respiratory Journal 05/2015; 45(6). DOI:10.1183/09031936.00229114 · 7.13 Impact Factor
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    ABSTRACT: Although the number of identified avian-borne picornaviruses (family Picornaviridae) is continuously increasing there remains several species-rich avian host groups, such as the order Falconiformes (with 290 bird species) from which picornaviruses have not been identified. This study reports the first complete genome of a novel, highly divergent picornavirus, named as Falcovirus A1 (KP230449), from the carnivorous bird, the common kestrel (Falco tinnunculus, order Falconiformes). Falcovirus A1 has the longest 3D(RdRp) genome region and distant phylogenetic relationship to the Hepatitis A virus 1 (Hepatovirus) and Avian encephalomyelitis virus 1 (Tremovirus). It has a type-I (enterovirus-like) IRES in the 5'UTR - identified for the first time among avian-borne picornaviruses suggesting that type-I IRES is not restricted only to enteroviruses and providing further evidence of mosaicism of this region among different picornavirus genera. Copyright © 2015. Published by Elsevier B.V.
    Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 04/2015; 32. DOI:10.1016/j.meegid.2015.04.005 · 3.26 Impact Factor
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    Emerging Infectious Diseases 04/2015; 21(4):713-715. DOI:10.3201/eid2104.141545 · 7.33 Impact Factor
  • Peter Simmonds
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    ABSTRACT: During infection, viruses generate copies of their genome and cause illness. For RNA viruses, replication is influenced by the frequencies of certain dinucleotides (CpG, UpA). Prof Simmonds reasons that dinucleotides may be therefore be targets of the innate immune response and has shown that manipulating their frequency is a viable strategy to create effective non-reverting attenuated viral vaccines, and improve production yields of inactivated vaccines through enhancing virus replication.
    American Association for the Advancement of Science 2014 Annual Meeting; 02/2015
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    ABSTRACT: Coxsackievirus A6 (CAV6) is an enterically transmitted enterovirus. Until recently, CAV6 infections have been considered as being of minor clinical significance and only rarely aetiologically linked with hand, foot and mouth disease (HFMD) associated with other species A enteroviruses (particularly enterovirus 71 and CAV16). From 2008 onwards, however, CAV6 infections have been associated with several outbreaks worldwide of atypical HFMD (aHFMD) accompanied by a varicelliform rash. We recently reported CAV6-associated eczema herpeticum (EH) occurring predominantly in children and young adults in Edinburgh in January - February, 2014. To investigate genetic determinants of novel clinical phenotypes of CAV6, we genetically characterised and analysed CAV6 variants associated with EH in Edinburgh, 2014 and those with aHFMD in CAV isolates collected from 2008. A total of eight recombinant forms have circulated worldwide over the past 10 years, with particularly recent appearance of recombinant form H (RF-H) associated with EH cases in Edinburgh in 2014. Comparison of phylogenies and divergence of complete genome sequences of CAV6 identified recombination breakpoints in 2A-2C, within VP3 and between VP1 and the 5'untranslated region. A Bayesian temporal reconstruction of CAV6 evolution since 2004 provided estimates of dates and the actual recombination events that generated more recently appearing RFs (-E, -F, -G and -H). Associations were observed between recombination groups and clinical presentations of herpangina, aHFMD and EH, but not with VP1 or other structural genes. These observations provide evidence that NS gene regions may potentially contribute to clinical phenotypes and outcomes of CAV6 infection.
    Journal of General Virology 01/2015; 96(Pt_5). DOI:10.1099/vir.0.000062 · 3.53 Impact Factor
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    ABSTRACT: HCV genotype 4 is prevalent in many African countries, yet little is known about the genotype׳s epidemic history on the continent. We present a comprehensive study of the molecular epidemiology of genotype 4. To address the deficit of data from the Democratic Republic of the Congo (DRC) we PCR amplified 60 new HCV isolates from the DRC, resulting in 33 core- and 48 NS5B-region sequences. Our data, together with genotype 4 database sequences, were analysed using Bayesian phylogenetic approaches. We find three well-supported intra-genotypic lineages and estimate that the genotype 4 common ancestor existed around 1733 (1650–1805). We show that genotype 4 originated in central Africa and that multiple lineages have been exported to north Africa since ~1850, including subtype 4a which dominates the epidemic in Egypt. We speculate on the causes of the historical intra-continental spread of genotype 4, including population movements during World War 2.
    Virology 01/2015; 464-465. DOI:10.1016/j.virol.2014.07.006 · 3.35 Impact Factor
  • Troels K H Scheel, Peter Simmonds, Amit Kapoor
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    ABSTRACT: Recent advances in sequencing technologies have greatly enhanced our abilities to identify novel microbial sequences. Thus, our understanding of the global virome and the virome of specific host species in particular is rapidly expanding. Identification of animal viruses is important for understanding animal disease, the origin and evolution of human viruses, as well as zoonotic reservoirs for emerging infections. Although the human hepacivirus, hepatitis C virus (HCV), was identified 25years ago, its origin has remained elusive. In 2011, the first HCV homolog was reported in dogs but subsequent studies showed the virus to be widely distributed in horses. This indicated a wider hepacivirus host range and paved the way for identification of rodent, bat and non-human primate hepaciviruses. The equine non-primate hepacivirus (NPHV) remains the closest relative of HCV and is so far the best characterized. Identification and characterization of novel hepaciviruses may in addition lead to development of tractable animal models to study HCV persistence, immune responses and pathogenesis. This could be particular important, given the current shortage of immunocompetent models for robust HCV infection. Much remains to be learned on the novel hepaciviruses, including their association with disease, and thereby how relevant they will become as HCV model systems and for studies of animal disease. This review discusses how virome analysis led to identification of novel hepaci- and pegiviruses, their genetic relationship and characterization and the potential use of animal hepaciviruses as models to study hepaciviral infection, immunity and pathogenesis. This article forms part of a symposium in Antiviral Research on "Hepatitis C: Next steps toward global eradication." Copyright © 2014. Published by Elsevier B.V.
    Antiviral Research 12/2014; 115. DOI:10.1016/j.antiviral.2014.12.014 · 3.43 Impact Factor
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    ABSTRACT: Mutating RNA virus genomes to alter codon pair (CP) frequencies and reduce translation efficiency has been advocated as a method to generate safe, attenuated virus vaccines. However, selection for disfavoured CPs leads to unintended increases in CpG and UpA dinucleotide frequencies that also attenuate replication. We designed and phenotypically characterised mutants of the picornavirus, echovirus 7, in which these parameters were independently varied to determine which most influenced virus replication. CpG and UpA dinucleotide frequencies primarily influenced virus replication ability while no fitness differences were observed between mutants with different CP usage where dinucleotide frequencies were kept constant. Contrastingly, translation efficiency was unaffected by either CP usage or dinucleotide frequencies. This mechanistic insight is critical for future rational design of live virus vaccines and their safety evaluation; attenuation is mediated through enhanced innate immune responses to viruses with elevated CpG/UpA dinucleotide frequencies rather the viruses themselves being intrinsically defective.
    eLife Sciences 12/2014; 3. DOI:10.7554/eLife.04531 · 8.52 Impact Factor
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    ABSTRACT: Introduction PARV4 is a parvovirus that was first identified in 2005 from the blood of an injecting drug user. It has now been well characterized in Western cohorts, where it is almost exclusively found in individuals with risk factors for blood-borne viruses (BBVs), and is strongly associated with Hepatitis C (HCV) and HIV infection. The epidemiology is strikingly different in Africa, where rates of PARV4 IgG antibody are 20-40% irrespective of risk factors for – or the presence of – other BBVs. The clinical consequences of PARV4 remain uncertain. A small number of studies have associated it with a variety of syndromes, including increased rate of progression to AIDS. Virological and immunological data suggest the virus may persist in a chronic latent form, with the potential for subsequent reactivation and long-term sequelae. Characterising PARV4 in Africa is crucial given its endemicity: in particular, transmission routes and clinical impact remain to be elucidated. Scientific findings We set out to study a cohort of mothers and children in Kimberley, South Africa, in order to characterize the epidemiology of PARV4 in this setting, and to investigate the impact of coinfection with HIV. We investigated a total of 157 individuals recruited via paediatric HIV clinics, as follows: HIV-infected children (n=90), HIV-infected mothers (n=43), and HIV-negative siblings (n=24). We used ELISA to detect IgG antibodies to PARV4 and to determine HBsAg status. We detected PARV4 IgG in 58/157 of these individuals (37%). There was an increase in IgG seroprevalence with age (R 2 =0.59, p=0.025, linear regression), suggesting ongoing transmission events that start in early childhood and continue among adolescents and young adults. There was no concordance in PARV4 IgG status between mothers and children, and PARV4 IgG was not enriched in either HIV or HBV-infected individuals. There was no effect of PARV4 IgG on either CD4 T cell count or viral load in HIV-infected adults or children.
    Federation of Infection Societies Meeting; 11/2014
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    ABSTRACT: Little is known about the tissue tropism of KI polyomavirus (KIPyV), and there are no studies to date describing any specific cell types it infects. The limited knowledge of KIPyV tropism has hindered study of this virus and understanding of its potential pathogenesis in humans. We describe tissues from two immunocompromised patients that stained positive for KIPyV antigen using a newly developed immunohistochemical assay targeting the KIPyV VP1 (KVP1) capsid protein. In the first patient, a pediatric bone marrow transplant recipient, KVP1 was detected in lung tissue. Double immunohistochemical staining demonstrated that approximately 50% of the KVP1-positive cells were CD68-positive cells of the macrophage/monocyte lineage. In the second case, an HIV-positive patient, KVP1 was detected in spleen and lung tissues. These results provide the first identification of a specific cell type in which KVP1 can be detected and expand our understanding of basic properties and in vivo tropism of KIPyV.
    Virology 11/2014; s 468–470:178–184. DOI:10.1016/j.virol.2014.08.005 · 3.28 Impact Factor
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    ABSTRACT: We describe the burden of influenza B infections in Scotland during a 13-year study period. Influenza A and B viruses cocirculated throughout the period, with numbers of influenza B cases approaching or exceeding those of influenza A during six influenza seasons. Influenza B viruses of both Victoria and Yamagata lineage were detected in two of six seasons investigated. For the 2012/13 season, influenza B accounted for 44.4% of all influenzas, with the highest incidence in those under the age of five years. Influenza B virus infections led to fewer admissions to an intensive care unit (ICU) and a lower mortality rate than influenza A (37 vs 81 ICU admissions and three vs 29 deaths) during the 2012/13 season. However, a quarter of those admitted to ICU with influenza B had not been immunised and 60% had not received specific influenza antiviral therapy. This highlights the need for consistent influenza vaccination and prompt usage of antiviral treatment for identified risk groups. Combining the newly introduced vaccination programme for children with the use of a tetravalent vaccine may provide the opportunity to improve the control of influenza B in those with the highest influenza B burden, children and young adolescents.
    Eurosurveillance: bulletin europeen sur les maladies transmissibles = European communicable disease bulletin 09/2014; 19(37):pii=20903. DOI:10.2807/1560-7917.ES2014.19.37.20903 · 4.66 Impact Factor
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    ABSTRACT: Norway rats (Rattus norvegicus) are globally distributed and concentrate in urban environments, where they live and feed in closer proximity to human populations than most other mammals. Despite the potential role of rats as reservoirs of zoonotic diseases, the microbial diversity present in urban rat populations remains unexplored. In this study, we used targeted molecular assays to detect known bacterial, viral, and protozoan human pathogens and unbiased high-throughput sequencing to identify novel viruses related to agents of human disease in commensal Norway rats in New York City. We found that these rats are infected with bacterial pathogens known to cause acute or mild gastroenteritis in people, including atypical enteropathogenic Escherichia coli, Clostridium difficile, and Salmonella enterica, as well as infectious agents that have been associated with undifferentiated febrile illnesses, including Bartonella spp., Streptobacillus moniliformis, Leptospira interrogans, and Seoul hantavirus. We also identified a wide range of known and novel viruses from groups that contain important human pathogens, including sapoviruses, cardioviruses, kobuviruses, parechoviruses, rotaviruses, and hepaciviruses. The two novel hepaciviruses discovered in this study replicate in the liver of Norway rats and may have utility in establishing a small animal model of human hepatitis C virus infection. The results of this study demonstrate the diversity of microbes carried by commensal rodent species and highlight the need for improved pathogen surveillance and disease monitoring in urban environments.
    mBio 08/2014; 5(5). DOI:10.1128/mBio.01933-14 · 6.88 Impact Factor
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    ABSTRACT: The family Hepeviridae consists of positive-stranded RNA viruses that infect a wide range of mammalian species, as well as chickens and trout. A subset of these viruses infects humans and can cause a self-limiting acute hepatitis that may become chronic in immunosuppressed individuals. Current published descriptions of the taxonomical divisions within the family Hepeviridae are contradictory in relation to the assignment of species and genotypes. Through analysis of existing sequence information, we propose a taxonomic scheme in which the family is divided into the genera Orthohepevirus (all mammalian and avian hepatitis E virus (HEV) isolates) and Piscihepevirus (cutthroat trout virus). Species within the genus Orthohepevirus are designated Orthohepevirus A (isolates from human, pig, wild boar, deer, mongoose, rabbit and camel), Orthohepevirus B (isolates from chicken), Orthohepevirus C (isolates from rat, greater bandicoot, Asian musk shrew, ferret and mink) and Orthohepevirus D (isolates from bat). Proposals are also made for the designation of genotypes within the human and rat HEVs. This hierarchical system is congruent with hepevirus phylogeny, and the three classification levels (genus, species and genotype) are consistent with, and reflect discontinuities in the ranges of pairwise distances between amino acid sequences. Adoption of this system would include the avoidance of host names in taxonomic identifiers and provide a logical framework for the assignment of novel variants.
    Journal of General Virology 07/2014; 95(Pt 10). DOI:10.1099/vir.0.068429-0 · 3.53 Impact Factor
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    ABSTRACT: Objectives Enteroviruses (EV) and human parechoviruses (HPeV) infections are increasingly indentified in neonates and young children with sepsis, meningitis and encephalitis. We investigated EV and HPeV viral loads in plasma and cerebrospinal fluid (CSF) among those presenting with sepsis or central nervous system (CNS) disease to gain understanding of the nature of these infections. Methods Detections frequencies and viral loads of EV and HPeV RNA were compared in plasma and CSF obtained from infected children originally identified on sepsis or CNS screening. Results Two distinct infection profiles were identified; 11 subjects with CNS disease, showed higher or similar viral loads in CSF than in plasma (median plasma:CSF ratio 0.5), whereas 14 children with sepsis showed low or undetectable viral loads in CSF and high viral loads in plasma (mean ratio 5,700). HPeV type 3 and one EV serotype (coxsackievirus B2) were primarily associated with the latter presentation. Conclusions Simple detection of EV or HPeV RNA in CSF is not predictive of CNS disease, especially in the absence of clinical markers (i.e. pleocytosis). Screening of plasma can identify EV and HPeV RNA in a substantial proportion of sepsis cases, some of which will be missed if CSF samples alone are screened.
    The Journal of infection 07/2014; 69(1). DOI:10.1016/j.jinf.2014.02.017 · 4.02 Impact Factor
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    Donald B Smith, Peter Simmonds
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    ABSTRACT: Background & AimsFulminant hepatitis is a rare outcome of infection with hepatitis E virus. Several recent reports suggest that virus variation is an important determinant of disease progression. To critically examine the evidence that virus-specific factors underlie the development of fulminant hepatitis following hepatitis E virus infection.Methods Published sequence information of hepatitis E virus isolates from patients with and without fulminant hepatitis was collected and analysed using statistical tests to identify associations between virus polymorphisms and disease outcome.ResultsFulminant hepatitis has been reported following infection with all four hepatitis E virus genotypes that infect humans comprising multiple phylogenetic lineages within genotypes 1, 3 and 4. Analysis of virus sequences from individuals infected by a common source did not detect any common substitutions associated with progression to fulminant hepatitis. Re-analysis of previously reported associations between virus substitutions and fulminant hepatitis suggests that these were probably the result of sampling biases.Conclusions Host-specific factors rather than virus genotype, variants or specific substitutions appear to be responsible for the development of fulminant hepatitis.
    Liver international: official journal of the International Association for the Study of the Liver 06/2014; 35(4). DOI:10.1111/liv.12629 · 4.41 Impact Factor
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    ABSTRACT: Non-primate hepacivirus (NPHV), equine pegivirus (EPgV) and Theiler's disease associated virus (TDAV) are newly discovered members of two genera in the Flaviviridae family, Hepacivirus and Pegivirus respectively, that include human hepatitis C virus (HCV) and human pegivirus (HPgV). To investigate their epidemiology, persistence and clinical features of infection, large cohorts of horses and other mammalian species were screened for NPHV, EPgV and TDAV viraemia and for past exposure through serological assays for NPHV and EPgV-specific antibodies. NPHV antibodies were detected in 43% of 328 horses screened for antibodies to NS3 and core antibodies, of which three were viraemic by PCR. All five horses that were stablemates of a viraemic horse were seropositive, as was a dog on the same farm. With this single exception, all other species were negative for NPHV antibodies and viraemia (donkeys (n=100), dogs (n=112), cats (n=131), non-human primates (n=164) and humans (n=362). EPgV antibodies to NS3 were detected in 66.5% of horses, including 11 of the 12 horses that had EPgV viraemia. All donkey samples were negative for EPgV antibody and RNA. All horse and donkey samples were negative for TDAV RNA. By comparing viraemia frequencies in horses with and without liver disease, no evidence was obtained that supported an association between active NPHV and EPgV infections with hepatopathy. The study demonstrates that NPHV and EPgV infections are widespread and enzootic in the study horse population and confirms that NPHV and potentially EPgV have higher frequencies of viral clearance than HCV and HPgV infections in humans.
    Journal of General Virology 05/2014; DOI:10.1099/vir.0.065094-0 · 3.53 Impact Factor
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    ABSTRACT: Enterovirus (EV) infections are associated with a wide array of often severe disease presentations including aseptic meningitis, encephalitis, and acute flaccid paralysis. Surveillance for polioviruses and other EVs is therefore important as a public health measure both for patient management and epidemiological studies. From 1988 to 2008, echovirus (E) 30 was the predominant genotype in Spain (33.7% of the total typed EVs). E6 was also endemic throughout this period although isolated less frequently (12.5%). In 2009, however, a substantial increase in the incidence of E6 was detected (60%), displacing E30 type (2%). To investigate the evolution and recombination in the epidemiology and transmission of E6 in Spain, a genetic analysis in VP1 and 3Dpol regions of 67 Spanish strains collected during the period 2004-2010 was performed. All VP1 sequences clustered monophyletically in the assigned genogroup C, subgroup 9, currently the predominant circulating strains identified in Europe and elsewhere in the last 10 years. 3Dpol sequences were interspersed with other species B EVs resulting from several recombination events that generated at least 12 different recombinant forms (RFs) among study samples. These showed typically minimal divergence in VP1. The co-circulation of different lineages of E6 in the same geographical area associated with its mainly endemic pattern of transmission may have contributed to the extremely short estimated half-life of E6 RFs (0.87 years). This pattern contrasts markedly with other species B EVs and EV71 where VP1 lineage expansion and extinction occurred in step with defined recombination events and periodic changes in incidence. J. Med. Virol.. © 2013 Wiley Periodicals, Inc.
    Journal of Medical Virology 05/2014; 86(5). DOI:10.1002/jmv.23741 · 2.22 Impact Factor
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    PLoS Pathogens 05/2014; 10(5):e1004036. DOI:10.1371/journal.ppat.1004036 · 8.06 Impact Factor
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    ABSTRACT: Anelloviruses are a family of small single stranded circular DNA viruses with a vast genetic diversity. Human infections with the prototype anellovirus, torque teno virus (TTV), are ubiquitous and related viruses have been described in a number of other mammalian hosts. Despite over 15 years of investigation, however, there is still little known about the pathogenesis and possible disease associations of anellovirus infections, arising in part due to the lack of a robust cell culture system for viral replication or tractable small animal model. We report the identification of diverse anelloviruses in several species of wild rodents. The viruses are highly prevalent in wood mice (Apodemus sylvaticus) and field voles (Microtus agrestis), detectable at a low frequency in bank voles (Myodes glareolus) but absent from house mice (Mus musculus). The viruses identified have a genomic organisation consistent with other anelloviruses but form two clear phylogenetic groups that are as distinct from each other as from defined genera.
    Journal of General Virology 04/2014; 95(Pt 7). DOI:10.1099/vir.0.065219-0 · 3.53 Impact Factor
  • Eurosurveillance: bulletin europeen sur les maladies transmissibles = European communicable disease bulletin 04/2014; 19(15). DOI:10.2807/1560-7917.ES2014.19.15.20772 · 4.66 Impact Factor

Publication Stats

23k Citations
3,165.44 Total Impact Points

Institutions

  • 1985–2015
    • The University of Edinburgh
      • • Roslin Institute
      • • Centre for Immunity, Infection and Evolution
      • • Edinburgh Infectious Diseases
      • • Laboratory for Clinical and Molecular Virology
      • • Medical Genetics Unit
      • • Division of Genetics and Genomics
      Edinburgh, Scotland, United Kingdom
  • 2012
    • Children's Hospital Los Angeles
      • Division of Hematology-Oncology
      Los Angeles, California, United States
    • The University of Warwick
      • School of Life Sciences
      Coventry, ENG, United Kingdom
  • 2010–2012
    • Columbia University
      • Center for Infection and Immunity
      New York City, New York, United States
    • National Institute for Health and Welfare, Finland
      Helsinki, Southern Finland Province, Finland
    • National Institute of Health Islamabad
      Islāmābād, Islāmābād, Pakistan
    • University of Iowa
      • Department of Internal Medicine
      Iowa City, IA, United States
  • 2011
    • University of Tartu
      • Institute of Technology
      Dorpat, Tartu County, Estonia
    • Shanghai Jiao Tong University
      Shanghai, Shanghai Shi, China
    • Instituto de Salud Carlos III
      Madrid, Madrid, Spain
    • Cornell University
      • College of Veterinary Medicine
      Ithaca, New York, United States
  • 2009
    • Los Alamos National Laboratory
      • Theoretical Biology and Biophysics Group
      Los Alamos, NM, United States
  • 2008–2009
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • Department of Medical Microbiology
      Amsterdam, North Holland, Netherlands
    • Stanford University
      • Division of Infectious Diseases
      Palo Alto, California, United States
    • Imperial College London
      Londinium, England, United Kingdom
    • University of Ottawa
      Ottawa, Ontario, Canada
  • 1998–2009
    • Chulalongkorn University
      • Faculty of Medicine
      Krung Thep, Bangkok, Thailand
  • 1995–2008
    • University of Bonn
      • Institute of Zoology
      Bonn, North Rhine-Westphalia, Germany
    • Royal Berkshire NHS Foundation Trust
      Reading, England, United Kingdom
    • Oxford University Hospitals NHS Trust
      • Department of Gastroenterology
      Oxford, ENG, United Kingdom
  • 2004–2006
    • University of Massachusetts Medical School
      • • Program in Molecular Medicine
      • • Department of Molecular Genetics and Microbiology
      Worcester, MA, United States
  • 1987–2006
    • University of Bristol
      • School of Chemistry
      Bristol, England, United Kingdom
  • 2005
    • Blood Systems Research Institute
      San Francisco, California, United States
  • 2001
    • The UK Clinical Virology Network
      Edinburgh, Scotland, United Kingdom
    • Ina Research Inc.
      Ina, Nagano, Japan
  • 1999
    • Guy's and St Thomas' NHS Foundation Trust
      Londinium, England, United Kingdom
  • 1997–1999
    • Oslo University Hospital
      • Department of Pathology
      Kristiania (historical), Oslo County, Norway
    • Aga Khan University Hospital, Karachi
      • Department of Medicine
      Karachi, Sindh, Pakistan
  • 1996
    • University of Florida
      • Department of Medicine
      Gainesville, FL, United States
    • University of California, San Francisco
      • Veterans Affairs Medical Center
      San Francisco, California, United States