P Simmonds

The University of Edinburgh, Edinburgh, Scotland, United Kingdom

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Publications (409)2835.44 Total impact

  • 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: 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; · 3.35 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. 12/2014; 3.
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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.
    Euro surveillance: bulletin europeen sur les maladies transmissibles = European communicable disease bulletin 09/2014; 19(37):pii=20903. · 5.49 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; · 3.13 Impact Factor
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    Donald B Smith, Peter Simmonds
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    ABSTRACT: Fulminant 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.
    Liver international: official journal of the International Association for the Study of the Liver 06/2014; · 3.87 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; · 3.13 Impact Factor
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    PLoS Pathogens 05/2014; 10(5):e1004036. · 8.14 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; · 3.13 Impact Factor
  • Euro surveillance: bulletin europeen sur les maladies transmissibles = European communicable disease bulletin 04/2014; 19(15). · 5.49 Impact Factor
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    ABSTRACT: SUMMARY To combat schistosomiasis, the World Health Organization (WHO) recommends that infection levels are determined prior to designing and implementing control programmes, as the treatment regimens depend on the population infection prevalence. However, the sensitivity of the parasitological infection diagnostic method is less reliable when infection levels are low. The aim of this study was to compare levels of Schistosoma haematobium infection obtained by the parasitological method vs serological technique. Infection levels in preschool and primary school-aged children and their implications for control programmes were also investigated. Infection prevalence based on serology was significantly higher compared with that based on parasitology for both age groups. The difference between infection levels obtained using the two methods increased with age. Consequentially, in line with the WHO guidelines, the serological method suggested a more frequent treatment regimen for this population compared with that implied by the parasitological method. These findings highlighted the presence of infection in children aged ⩽5 years, further reiterating the need for their inclusion in control programmes. Furthermore, this study demonstrated the importance of using sensitive diagnostic methods as this has implications on the required intervention controls for the population.
    Parasitology 03/2014; · 2.36 Impact Factor
  • Euro surveillance: bulletin europeen sur les maladies transmissibles = European communicable disease bulletin 03/2014; 19(12). · 5.49 Impact Factor
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    ABSTRACT: Enteroviruses (EVs) are a genetically and antigenically diverse group of viruses infecting humans. A mostly distinct set of EV variants have additionally been documented to infect wild apes and several, primarily captive, Old World monkey (OWM) species. To investigate the prevalence and genetic characteristics of EVs infecting OWMs in the wild, faecal samples from mandrills (Mandrillus sphinx) and other species collected in remote regions of Southern Cameroon were screened for EV RNA. Remarkably high rates of EV positivity were detected in M.sphinx (100 from 102 screened), Cercocebus torquatus (7/7) and Cercopithecus cephus (2/4), with high viral loads indicative of active infection. Genetic characterisation in VP4/VP2 and VP1 regions allowed EV variants to be assigned to simian species H (EV-H), EV-J (including one or more new types) while seven matched simian EV-B variants, SA5 and EV110 (chimpanzee). Sequences from the remaining 70 formed a new genetic group distinct in VP4/2 and VP1 region from all currently recognised human or simian EV species. Complete genome sequences were obtained from three to determine their species assignment. In common with EV-J and the EV-A A13 isolate, new group sequences were chimaeric, being most closely related to EV-A in capsid genes and to EV-B in the non-structural gene region. Further recombination events created different groupings in 5' and 3' untranslated regions. While clearly a distinct EV group, the hybrid nature of new variants prevented their unambiguous classification as either members of a new species or as divergent members of EV-A using current ICTV assignment criteria. This study is the first large scale investigation of the frequency of infection and diversity of enteroviruses (EVs) infecting monkeys (primarily mandrills) in the wild. Findings demonstrate extremely high frequencies of active infection (95%) among mandrills and other Old World monkey species inhabiting remote regions of Cameroon without human contact. EV variants detected were distinct from those infecting human populations, comprising members of enterovirus species B, J and H and a large novel group of viruses that potentially represent a candidate new EV species. The viral sequences obtained contribute substantially to our growing understanding of the genetic diversity of EVs and the existence of inter-species chimaerism that characterises the novel variants in the current study, as well as in previously characterised species A and J viruses infecting monkeys. The latter findings will contribute to future development of consensus criteria for species assignments in enteroviruses and other picornavirus genera.
    Journal of Virology 03/2014; · 5.08 Impact Factor
  • Transfusion 03/2014; 54(3):744-5. · 3.53 Impact Factor
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    ABSTRACT: Most RNA viruses infecting mammals and other vertebrates show profound suppression of CpG and UpA dinucleotide frequencies. To investigate this functionally, mutants of the picornavirus, echovirus 7 (E7), were constructed with altered CpG and UpA compositions in two 1.1-1.3 Kbase regions. Those with increased frequencies of CpG and UpA showed impaired replication kinetics and higher RNA/infectivity ratios compared with wild-type virus. Remarkably, mutants with CpGs and UpAs removed showed enhanced replication, larger plaques and rapidly outcompeted wild-type virus on co-infections. Luciferase-expressing E7 sub-genomic replicons with CpGs and UpAs removed from the reporter gene showed 100-fold greater luminescence. E7 and mutants were equivalently sensitive to exogenously added interferon-β, showed no evidence for differential recognition by ADAR1 or pattern recognition receptors RIG-I, MDA5 or PKR. However, kinase inhibitors roscovitine and C16 partially or entirely reversed the attenuated phenotype of high CpG and UpA mutants, potentially through inhibition of currently uncharacterized pattern recognition receptors that respond to RNA composition. Generating viruses with enhanced replication kinetics has applications in vaccine production and reporter gene construction. More fundamentally, the findings introduce a new evolutionary paradigm where dinucleotide composition of viral genomes is subjected to selection pressures independently of coding capacity and profoundly influences host-pathogen interactions.
    Nucleic Acids Research 01/2014; · 8.81 Impact Factor
  • Donald B Smith, Peter Simmonds, Jeanne E Bell
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    ABSTRACT: The long-term impact of chronic human immunodeficiency virus (HIV) infection on brain status in injecting drug users (IDU) treated with highly active antiretroviral therapy (HAART) is unknown. Viral persistence in the brain with ongoing neuroinflammation may predispose to Alzheimer-like neurodegeneration. In this study, we investigated the brains of ten HAART-treated individuals (six IDU and four non-DU), compared with ten HIV negative controls (six IDU and four non-DU). HIV DNA levels in brain tissue were correlated with plasma and lymphoid tissue viral loads, cognitive status, microglial activation and Tau protein and amyloid deposition. Brain HIV proviral DNA levels were low in most cases but higher in HIV encephalitis (n = 2) and correlated significantly with levels in lymphoid tissue (p = 0.0075), but not with those in plasma. HIV positive subjects expressed more Tau protein and amyloid than HIV negative controls (highest in a 58 year old), as did IDU, but brain viral loads showed no relation to Tau and amyloid. Microglial activation linked significantly to HIV positivity (p = 0.001) and opiate abuse accentuated these microglial changes (p = 0.05). This study confirms that HIV DNA persists in brains despite HAART and that opiate abuse adds to the risk of brain damage in HIV positive subjects. Novel findings in this study show that (1) plasma levels are not a good surrogate indicator of brain status, (2) viral burden in brain and lymphoid tissues is related, and (3) while Tau and amyloid deposition is increased in HIV positive IDU, this is not specifically related to increased HIV burden within the brain.
    Journal of NeuroVirology 01/2014; · 2.85 Impact Factor
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    ABSTRACT: The epidemiology of viral hepatitis has changed. Since the introduction of safe and effective vaccines for hepatitis A and B in 1980s, the incidence of acute infections caused by these viruses has been declining in the UK. At the same time, hepatitis E virus (HEV) has been recognised as an increasingly important cause of acute hepatitis, but testing is not widely available. The aim of this study was to establish the viral causes of acute hepatitis, and use that data to modify the current diagnostic algorithm. A Cognos search was performed to collate subjects tested for HAV, HBV, HCV, HEV, EBV and CMV between June 2010 and December 2012. Information included virological result and their ALT level if done within 5 days from virological testing. From 3462 subjects with suspected acute viral hepatitis, only 25% had biochemical evidence of acute hepatitis (n=854; ALT>100IU/l). The frequency of detection of acute HEV infection (25/409) was over 31-times higher than that of HAV (6/3462), and 7-times higher than that of HBV (24/3462). Most cases of acute HAV, HEV, EBV and CMV infections presented with abnormal ALT levels. Most EBV infections were associated with lymphadenopathy (23/34); in comparison most of CMV infections were not associated with lymphadenopathy (18/22). HEV screening should be included in the initial testing panel for acute hepatitis and screening at least for HAV and HEV might be limited to those with abnormal ALT levels.
    Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 01/2014; · 3.12 Impact Factor
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    ABSTRACT: The 2005 consensus proposal for the classification of hepatitis C virus (HCV) presented an agreed and uniform nomenclature for HCV variants and the criteria for their assignment into genotypes and subtypes. Since its publication, the available dataset of HCV sequences has vastly expanded through advancement in nucleotide sequencing technologies and an increasing focus on the role of HCV genetic variation in disease and treatment outcomes. The current study represents a major update to the previous consensus HCV classification, incorporating additional sequence information derived from over 1,300 (near-)complete genome sequences of HCV available on public databases in May 2013. Analysis resolved several nomenclature conflicts between genotype designations and using consensus criteria created a classification of HCV into seven confirmed genotypes and 67 subtypes. There are 21 additional complete coding region sequences of unassigned subtype. The study additionally describes the development of a Web resource hosted by the International Committee for Taxonomy of Viruses (ICTV) that maintains and regularly updates tables of reference isolates, accession numbers, and annotated alignments (http://talk.ictvonline.org/links/hcv/hcv-classification.htm). The Flaviviridae Study Group urges those who need to check or propose new genotypes or subtypes of HCV to contact the Study Group in advance of publication to avoid nomenclature conflicts appearing in the literature. While the criteria for assigning genotypes and subtypes remain unchanged from previous consensus proposals, changes are proposed in the assignment of provisional subtypes, subtype numbering beyond “w,” and the nomenclature of intergenotypic recombinant. Conclusion: This study represents an important reference point for the consensus classification of HCV variants that will be of value to researchers working in clinical and basic science fields. (Hepatology 2014;59:318-327)
    Hepatology 01/2014; 59(1). · 12.00 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 01/2014; · 4.13 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 01/2014; 5(5). · 6.88 Impact Factor

Publication Stats

19k Citations
2,835.44 Total Impact Points

Institutions

  • 1985–2014
    • The University of Edinburgh
      • • 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
  • 2013
    • Royal Society of Edinburgh
      Edinburgh, Scotland, United Kingdom
    • The Rockefeller University
      • Laboratory of Virology and Infectious Disease
      New York City, New York, United States
  • 2010–2013
    • Columbia University
      • Center for Infection and Immunity
      New York City, NY, United States
    • National Institute for Health and Welfare, Finland
      Helsinki, Southern Finland Province, Finland
    • National Institute of Health Islamabad
      Islāmābād, Islāmābād, Pakistan
  • 2005–2013
    • University of Oxford
      • • Nuffield Department of Clinical Medicine
      • • Department of Zoology
      Oxford, ENG, United Kingdom
  • 1996–2013
    • Instituto de Salud Carlos III
      • Center National of Microbiology (CNM)
      Madrid, Madrid, Spain
    • University of Florida
      • Department of Medicine
      Gainesville, FL, United States
    • University of Milan
      • Department of Internal Medicine
      Milano, Lombardy, Italy
  • 2012
    • Children's Hospital Los Angeles
      Los Angeles, California, United States
    • Université de Sherbrooke
      • Department of Microbiology and Infectious Diseases
      Sherbrooke, Quebec, Canada
  • 2008–2012
    • The University of Warwick
      • • School of Life Sciences
      • • Biological Sciences
      Coventry, ENG, United Kingdom
    • National University of Ireland, Galway
      Gaillimh, Connaught, Ireland
    • University of Ottawa
      Ottawa, Ontario, Canada
    • Stanford University
      • Division of Infectious Diseases
      Palo Alto, California, United States
  • 2004–2012
    • University of Massachusetts Medical School
      • • Department of Microbiology and Physiological Systems
      • • Center for AIDS Research
      • • Program in Molecular Medicine
      • • Department of Molecular Genetics and Microbiology
      Worcester, MA, United States
  • 2011
    • University of Tartu
      • Institute of Technology
      Dorpat, Tartu County, Estonia
    • University of Cambridge
      Cambridge, England, United Kingdom
    • Shanghai Jiao Tong University
      Shanghai, Shanghai Shi, China
    • Cornell University
      • College of Veterinary Medicine
      Ithaca, New York, United States
  • 2010–2011
    • University of Iowa
      • Department of Internal Medicine
      Iowa City, IA, United States
  • 2009–2010
    • University of California, San Francisco
      • Department of Laboratory Medicine
      San Francisco, CA, United States
  • 2008–2009
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • Department of Medical Microbiology
      Amsterdam, North Holland, Netherlands
  • 2006–2009
    • Los Alamos National Laboratory
      • Theoretical Biology and Biophysics Group
      Los Alamos, NM, United States
    • Western General Hospital
      Edinburgh, Scotland, United Kingdom
  • 1998–2009
    • Chulalongkorn University
      • Faculty of Medicine
      Krung Thep, Bangkok, Thailand
  • 1995–2008
    • University of Bonn
      • • Institute of Zoology
      • • Institute of Medical Microbiology, Immunology and Parasitology
      Bonn, North Rhine-Westphalia, Germany
    • Oxford University Hospitals NHS Trust
      • Department of Gastroenterology
      Oxford, ENG, United Kingdom
  • 1987–2004
    • University of Bristol
      • School of Chemistry
      Bristol, England, United Kingdom
  • 2001
    • The UK Clinical Virology Network
      Edinburgh, Scotland, United Kingdom
  • 1995–2000
    • Dokuz Eylul University
      Ismir, İzmir, Turkey
  • 1999
    • International Center for Research on Women
      Washington, Washington, D.C., United States
    • Guy's and St Thomas' NHS Foundation Trust
      Londinium, England, United Kingdom
  • 1996–1999
    • Oslo University Hospital
      Kristiania (historical), Oslo County, Norway
  • 1997
    • Aga Khan University Hospital, Karachi
      • Department of Medicine
      Karachi, Sindh, Pakistan