Viral Zoonotics
The Laboratory of Viral Zoonotics (LVZ) focuses on cross species transmission of viruses, and the co-evolution of viruses and their hosts including the evolution of immune mechanisms of disease, disease resistance and prevention. Not only has this interest led to the discovery of a number of new viruses, the genetic comparison of host and viral sequences from the same individual and sample have provided powerful genetic tools to solve some of nature's intriguing mysteries. Currently this laboratory applies molecular technologies to address important questions concerning zoonotic infections of importance to both veterinary and human health. We designed and run the newest, state of the art Biocontainment laboratory (BSL3) at the University and operate a new multiparamenter Flow sorting facility for single cell sorting of infectious samples under BSL3 conditions. This new facility enables the isolation and direct sequencing of single cells of different types infected with a variety of different viral agents or transforming plasmids. There is full spectrum of Viral-Immunopathology projects, ranging from the evolution of Zoonotic pathogens, characterisation of the Virome in "One Health and Disease" and impact of viral infections in primary immunodeficiencies. Research in the LVZ is divided into 3 broad areas; genomics, viromics and immunity.
Studies also focus on understanding successful host immune responses to RNA viruses. Translationally this information is utilized for the rational design of novel vaccines for the prevention of diseases caused by notoriously variable viral pathogens. Within the "immunity" programme, the lab continues to address the complex issues of immune correlates and to develop strategies to systematically dissect vaccine-induced immune responses that facilitate vaccine efficacy. Current vaccine programmes include structure based vaccine development for HIV and hepatitis C, and rational vaccine design by escape analysis.
Facilities
We designed and run the newest, state of the art biological Containment Level 3 (CL3) laboratory at the University as well as operate a new multiparamenter Flow sorting facility for single cell sorting of infectious samples under CL3 conditions. This new facility enables the isolation and direct sequencing of single cells of different types infected with a variety of different viral agents or transforming plasmids. We have made both our CL3 facilities and FACS CL3 Suite available for use by members of the University.
Biography
I obtained my Doctorate in Veterinary Medicine from the Ontario Veterinary College in 1984. After an externship with Peter Kennedy at UC Davis, I decided to pursue pathology and trained under Ted Valli in anatomic and clinical pathology receiving a DVSc in Pathology from the U of Guelph (1986). Subsequently I moved from Canada to SJ O'Brien's lab at the NIH in Maryland where I completed my PhD on the oncogenic transformation of B-cells by a bovine retrovirus, BLV. I became interested in genetic susceptibility to infectious disease and stayed on for postdoctoral work with O'Brien where I studied an outbreak of Feline Infectious Peritonitis virus in Cheetahs. I then moved to California as a Postdoctoral Fellow in Pathology at the Stanford School of Medicine to study a human cancer caused by HTLV-1, obtaining valuable technologies from the Crabtree (NFAT, T-cel activation) and Herzenberg (FACS) labs. After my fellowship in Human Pathology, I moved to study Transplant and retroviral disease pathology at TNO the Netherlands with P Bentvelzen and became interested in the origins of HIV and the challenge of how to design/develop a vaccine variable and immunosupressive viruses. I built and established my own lab, the Lab of Viral Pathogenesis at TNO which grew to become the Department of Virology which I headed for more than 10 years. After becoming an associate Professor at the University of Leiden, in 2007 I moved to Cambridge to start the Lab of Viral Zoonotics. I am a Member of the Royal College of Veterinary Surgeons, Fellow of the Linnean Society, the Royal College of Medicine, and Fellow of the Royal College of Pathologists. In 2012 I received an ScD from the University of Cambridge for my work in Viral Immunology and Immunopathology. In 2014 I organised the University wide multidisiplinary Darwin College Lecture series on "Plagues", not knowing that later in the year that the smouldering Ebola outbreak in West Africa would explode into a devastating epidemic.
Research
Lecture: One Health and the Future of the Veterinary Profession
Members of the Laboratory of Viral Zoonotics
- Simon Frost, University Senior Lecturer
- Barbara Blacklaws, University Senior Lecturer
- Gordon Daly, Post Doctoral Research Associate, Viral Discovery
- Eyal Maori, Marie Curie Fellow, Viral Integration, Viral Immunogenetics
- Amita Shortland, DVM, PhD (Cambridge), Murine viruses.
- David Seilly, Research Assistant protein chemistry and purification
- Sheryl Baptista, Research assistant, HIV vaccine evaluation, Arenaviruses.
- Samuel Stubbs, PhD student (MRC studentship), Virome/Microbiome in CVID patients
- Paul Tonks, BSL-3 Lab & Flow sorting Facilities, Vaccine studies coordinator
- James Chettle, PhD Student (Wellcome Trust) Murine Norovirus
- Osama Eisa, MD, PhD candidate (IB), Microbiome and pathogen resistance.
- Zaria Gorvett, MPhil candidate, Pathogenic origins of HIV-1
- A Chinedu Ugwu, DVA, Msc, PhD candidate, DCs and the Zoonotic origins of HIV-1
- Sarah Beerbower, PhD candidate, Viral activation and the GI microbiome
- Arden Dieker Viik, MPhil candidate, HIV-1 vaccine immune correlates
- Giacomo Gorini, MSc, PhD candidate (NIH), B-cell immune correlates of HIV vaccines.
Alumni of the LVZ
- Mariana Varela, Wellcome Trust Intermediate Fellow, Glasgow.
- Mark Sheperd, Research Associate (IT, UCS), Cambridge
- Lisa Landskron, (MSc/PhD, Vienna)
- Julia Weinelt, (MSc/PhD, Vienna)
- Rachel Lai, Post Doctoral Research Associate, (NIMR), Mill Hill, London, UK.
- Nick Bexfield BVetMed PhD (Cambridge) DSAM DipECVIM, Lecturer in Nottingham
- Tim Fitzmaurice, Research Associate, Dept of Medicine (Addenbrookes), Cambridge.
- Anna Albecka, Post Doctoral Research Associate, Dept. of Pathology, Cambridge..
- Judith Heaney, Post Doctoral Research Associate.
- Michele Lai, Research Assistant (now PhD student, Univ. of Genoa).
- Rosie Hancock, Veterinary student Cambridge
- Ishla Seager, Ireland
- Aurélien Simona, MD, (MSc at LVZ) now doing Immunology & infectious disease training at U of Geneva
- Antonia Meyer, Germany.
- Martina Schneider, (MSc at LVZ), now PhD candidate (Vienna)
- Suzy Blows, HR & PA, Division of Cardiovascular Medicine, Addenbrookes Hospital, Cambridge.
- Hanna Dreja, Research Scientist, Abcam, Cambridge.
- Fabian Schmidt, Postdoc at the Aaron Diamond Research Center, New York.
- Mehran Bhatti, MPhil graduate now at Johnson & Johnson in Switzerland
- Ed Greenwood, Postdoc with the Lehner lab, CIMR Cambridge.
Funding and Support
- Innovate UK: Emerging Vaccine Antigen Insert Cassettes (EVAC)
- Innovate UK: Tri-Valent Lassa, Ebola Marburg Vaccine (Tri-LEMvac)
- The Wellcome Trust
- The Bill and Melinda Gates Foundation
- The National Institutes of Health
- The European Commission
- Kennel Club Charitable Trust
Main collaborators
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- Helen Baxendale, Consultant Immunologist Papworth Hospital
- Dinakantha Kumararatne, Consultant Immunologist, Addenbrooke's Hospital
- Ranier Doffinger, Dept of Clinical Biochemistry and Immunology, Addenbrooke's.
- Robin Weiss, University College London, UK
- Susan Barnett and colleagues, Novartis Vaccines and Diagnostics
- Giuseppe Pantaleo, CHUV, Lausanne, Switzerland
- Ralf Wagner, University of Regensburg, Germany
- William Bernal, Kings College London, UK
- Sheena McCormack, Clinical Trial Unit, London, UK
- Mariano Esteban, Centro Nacional de Biotecnologia, Madrid, Spain
- Quentin Sattentau, University of Oxford
- Mahima Swamy, U of Dundee and Adrian Hayday, King's College, London.
- Peter Liljestrom, Karolinska Institutet, Stockholn, Sweden
- Paul Kellam, Julian Parkhill and Gordon Dougan, Wellcome Trust Sanger Institute, Hinxton, Cambridge
- Winifred Weissenhorn, Joseph Fourier University, Grenoble, France
- Graeme Alexander, Cambridge University Hospital NHS Foundation Trust
- Ken Smith, Paul Lyons, Department of Medicine, University of Cambridge
- Paul Lehner, Gillian Griffiths, CIMR, Cambridge
- Leo James, LMB, Cambridge
- Marc Veldhoen, BBSRC Babraham, Cambridge.
- Jonathan Weber, Imperial College London
- Martin Curran, Suzy English, HPA Addenbrookes, Cambridge
- Mario Caccamo & Richard Leggett, TGAC, Norwich
- Marc Veldhoen, BBSRC Babraham Institute, Cambridge.
- Steven Holland, Lab of Clinical Infectious Diseases, NIAID, NIH Bethesda.
- Genoveffa Franchini, Vaccine Branch, NIH, NCI, Bethesda.
Publications
Google scholar - link to all publications
Edited by Jonathan L. Heeney & Sven Friedemann with contributions from Christopher Dobson, Mary Dobson, Sir Leszek Borysiewicz, Angela McLean, Stephen J. O'Brien, Ian Morris, Mikko Hypponen, Stephen Emmott, Rowan Williams
Cambridge University Press 2017.
Heeney JL. Ebola: Hidden reservoirs. Nature. 2015 Nov 26;527(7579):453-5.
Simian immunodeficiency virus infection of chimpanzees (Pan troglodytes) shares features of both pathogenic and non-pathogenic lentiviral infections Greenwood EJD, Schmidt F, Kondova I, Niphuis H, Hodara V, Clissold L, McLay K, Guerra B, Redrobe S, Giavedoni LD, Lanford RE, Murthy KK, Rouet F, Heeney JL PLOS Pathogens 2015. Sept. 11;11(9):e1005146.
Intestinal intraepithelial lymphocyte activation promotes innate antiviral resistance. Swamy M, Abeler-Dörner L, Chettle J, Mahlakõiv T, Goubau D, Chakravarty P, Ramsay G, Reis e Sousa C, Staeheli P, Blacklaws B, Heeney JL, and Hayday A. Nature Comm. 2015 May 19;6:7090.
Clearance of genotype 1b Hepatitis C Virus in chimpanzees in the presence of vaccine-induced E1-neutralizing antibodies Verstrepen, B.E., Depla, E., Rollier, C.S., Mares, G., Drexhage, J.A.R., Priem, S., Verschoor, E.J., Koopman, G., Granier, C., Dreux, M., Cosset, F.L., Maertens, G., Heeney, J.L.. Journal of Infectious Diseases. 2011 Sep 15;204(6):837-44.
Comparison of human and rhesus macaque T-cell responses elicited by boosting with NYVAC encoding HIV-1 clade C immunogens. Mooij, P., Balla-Jhagjhoorsingh, S.S., Beenhakker, N., van Haaften, P., Baak, I., Nieuwenhuis, I.G., Heidar, S., Wolf, H., Frachette, M-J., Bieler, K., Sheppard, N., Harari, A., Bart, P.A., Liljeström, P., Wagner, R., Pantaleo, G., Heeney, J.L. Journal of Virology. 2009 Jun; 83(11);5881-5889.
