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National Institute of Allergy and Infectious Diseases (NIAID)

Changing Host Ranges of Viruses Leading to Emergence of New Pathogens
September 6 – 8, 2005 Washington, DC


Agenda Participants Workshop Summary

Agenda

Tuesday, September 6
 
  Introduction
7:00 p.m. Introductory remarks (Buffet Dinner)
  Overview and introduction to the meeting; summary of the objectives; plan for the presentations and discussions
Steering Committee members and NIH representatives
7:30 p.m. Session I: Viral reservoirs in animals—the effects of human behavior and interactions with other animals or effects on the environment that can potentially result in new viral emergences
  Topics to consider:
  • Which animals are the potential sources of viruses that might emerge in humans or other animals?
  • What do we know about the importance of certain reservoir animals versus others? Is there anything in common about the reservoirs that have given rise to emerged viruses in humans or other animals that would allow us to evaluate relative risks?
  • What do we know about the evolutionary or epidemiological dynamics of viruses in their reservoirs?
  • What is the role (if any) of intermediate hosts between the reservoir and the final host (e.g., influenza: pigs or terrestrial birds; SARS: civet or other cats)?
  • What is the potential for control of emerging viruses in their reservoirs or reduction in possibility of spread to humans?

1) *Mark Woolhouse – University of Edinburgh, UK. Viral emergence and zoonosis.
2) Hu Zhihong - Wuhan Institute of Virology. SARS coronavirus and control of infection.
3) **Peter Daszak – Consortium for Conservation Medicine. Viruses (and other pathogens) in wildlife and emerging diseases.
 

Wednesday, November 7
 
8:30 a.m. Session II: Host-virus interactions at cellular, molecular, and/or receptor levels and the control of host range
  Topics to consider:
  • How do viruses change their basic host ranges in order to infect a new host species?
  • What molecular events allow viruses to become successfully adapted to a new host species?
  • The stages of transfer—is transfer of a low-efficiency virus followed by further adaptation?
  • How many changes (in how many genes) are required in the virus to allow the successful replication and spread?
  • What host barriers are overcome?
  • What is the effect on replication in the original (donor) host? Did this decrease as the virus adapted to the new (recipient) host?
4) Michael Farzan – Harvard University Medical School. SARS coronavirus and HIV receptors.
5) *Kathryn Holmes – University of Colorado Health Sciences Center. Coronavirus cell binding, entry, and host range.
6) Ralph Baric – University of North Carolina. Coronaviruses (and other RNA viruses) and cross species transmission.
7) Yoshihiro Kawaoka – University of Wisconsin, Madison. Influenza virus host range and adaptation.
8) X.J. Meng – Virginia Polytechnic Institute and State University and University of Maryland. Hepatitis E virus and porcine viruses.
9) **Colin Parrish – Cornell University. Parvovirus evolution and the control of host range.
10) Daniel Perez – University of Maryland. Influenza replication proteins.
11:00 a.m. Break
11:30 a.m. Session III: Adaptation to and pathogenesis in the new host; innate and adaptive host responses to viruses
  Topics to consider:
  • How do the host responses to viruses affect their susceptibility to infection or disease?
  • What is the role of innate immune responses to viruses? Can those distinguish between viruses from different hosts to determine their host ranges?
  • Viral anti-immune response genes and activities—host specificity and adaptation; roles in allowing the virus to replicate in the face of innate and adaptive immune responses from the original and the new hosts.
  • Effectiveness of the immune responses, the efficacy of vaccines developed to control the emerging viruses.
  • Host tissue specificity and the pathogenesis of the virus in the donor and recipient hosts—is there adaptation to new host tissues?
  • Avoidance of inhibition by host tissue and plasma components (e.g., serum inhibitors and lectins).
11) **Linda Saif – The Ohio State University. Coronaviruses and viral pathogenesis.
12) Lindsay Whitton – The Scripps Research Institute. Viral pathogenesis and antiviral immunity.
13) *Grant McFadden – Robarts Research Institute, University of Western Ontario. Poxvirus host interactions.
14) William Bellini – CDC. Paramyxovirus host adaptation and spread; SARS virus.
15) Liisa Selin – University of Massachusetts Medical School. Immune responses to viruses.
1:00 p.m. Buffet Lunch
2:00 p.m. Session IV: Viral evolution and the process of transfer and adaptation to new hosts
  Topics to consider:
  • Fundamental principles of virus evolution, particularly as they apply to the emergence of viruses and transfer across the host-species barrier.
  • The generation of diversity in viral genomes, including genomic sequence error rates and conservation or selection of viral sequences.
  • Comparison of large and small genome viruses as well as RNA, DNA, and retroviruses; common themes and differences among virus families; implications for potential host transfers.
  • Short-term acute infections versus long-term persistent/latent infections and the comparison of epidemic and endemic virus populations.
  • The special problem of transfer to new hosts—acquisition of variation in the donor host, transfer and founder effects, and post-transfer adaptation.
16) **Edward Holmes - Pennsylvania State University. Evolution and population genetics of viruses.
17) *Luis Villarreal – University of California, Irvine. Evolution of viral-host relationships.
18) Esteban Domingo – Universidad Autonoma de Madrid, Madrid, Spain. Virus evolution and variation.
4:00 p.m. Break
4:30 p.m. Session V: Acquiring high transmissibility among humans by viruses and epidemic spread; also insect vector adaptation of arboviruses
  Topics to consider:
  • Many viruses can replicate in new or alternative hosts without being able to spread efficiently to new host animals (dead end infections). What factors restrict host-host spread by those viruses?
  • What changes in the viruses permit efficient host-host spread?
  • How many steps are involved in this stage of host adaptation, and how much is known about the processes involved?
  • The role of virus and host specificity of insect vectors in allowing the efficient spread of arboviruses between different hosts.
19) Neil Ferguson – Imperial College, UK. Mathematical modeling of disease outbreaks.
20) *Don Burke – Johns Hopkins University. Public health and epidemiology.
19) James Koopman – University of Michigan. Epidemiology of infectious diseases.
20) Scott Layne - University of California, Los Angeles School of Public Health. Influenza and other emerging pathogens.
22) **Charles Calisher – Colorado State University. Virus epidemiology and arbovirus transmission.
 
Thursday, September 8
 
8:30 a.m. Session VI: The process of post-transfer adaptation: How do viruses become optimized for replication and transmission in the new host?
  Topics to consider:
  • Once a virus transfers to the new host and gains the ability to spread efficiently, a second stage of adaptation likely optimizes the virus for its new host. What do we know about this process?
  • Viral factors involved in the host optimization process and how do they (in some cases) work together; for example, the co-adaptation of two (or more) different viral proteins (such as the coordinated changes in the influenza HA and NA genes for binding and cleavage or of components of the replication complexes).
  • Role of multiple selections on the same gene/function, e.g., selection for antigenic variation and receptor binding on the same protein.
24) *Mark Pallansch – CDC Enterovirus Section. Virus evolution and adaptation strategies, poliovirus eradication.
25) **Jeff Taubenberger - Armed Forces Institute of Pathology. Emergence of influenza (H1N1) and host adaptation.
26) Wendy Barclay – University of Reading, UK. Influenza virus cell interactions.
27) Not yet confirmed from CDC – Influenza variation and host adaptation.
10:30 a.m. Break
11:00 a.m. Session VII: The epidemiology of new pathogens at different stages of the adaptation process. Infectious disease prevention and control strategies and their use in the cases of emerging epidemic viruses
  Topics to consider:
  • What are the most effective rapid methods for detecting new emerging viruses?
  • What infrastructure, people, or processes would allow earliest detection of new agents?
  • What are the most effective control strategies—considering the earliest stages of outbreak while still localized and the most effective once spread has started.
  • How does the adaptation process of the virus play into the control strategies—early less adapted versus later better adapted viruses?
  • The roles of vaccinations, drugs, emergency responses?
  • International coordination and planning—strategic considerations?
28) Stephen Morse – Columbia University. Planning and preparedness.
29) **C.J. Peters – University of Texas Medical Branch. Viral outbreaks, epidemiology, and public health.
30) *Lonnie King – Michigan State University & CDC. Emerging diseases and veterinary medicine.
31) Marc van Rengemortel – Biotechnology School of the University of Strasbourg, France. Virology and virus diseases.

  Session VIII Summary and conclusions

Everyone – overall discussion of the topics and issues. Panel summary to decide on the agreed strategies and any recommendations for further investigation; missing knowledge.


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Participants

Dr. Wendy S. Barclay
School of Animal and Microbial Sciences
University of Reading, UK

Dr. Ralph S. Baric
Associate Professor of Epidemiology and Microbiology
Department of Microbiology & Immunology
The University of North Carolina
Chapel Hill, NC 27599-7290

Dr. Barry J. Beaty
Department of Microbiology, Immunology, and Pathology
College of Veterinary Medicine & Biomedical Sciences
Colorado State University
Fort Collins, CO 80523

Dr. William J. Bellini
National Centers for Infectious Diseases
Division of Viral and Rickettsial Diseases
Respiratory and Enteric Virus Branch
Centers for Disease Control and Prevention
1600 Clifton Rd. NE, Mailstop G-09
Atlanta, GA 30333

Dr. Donald S. Burke
Professor/Associate Department Chair for Disease Prevention and Control
Johns Hopkins Bloomberg School of Public Health
615 N Wolfe Street, Room E5527
Baltimore, MD 21205

Dr. Charles H. Calisher
Department of Microbiology, Immunology, and Pathology
College of Veterinary Medicine & Biomedical Sciences
Colorado State University
Fort Collins, CO 80523

Dr. Peter Daszak
Executive Director
Consortium for Conservation Medicine,
460 West 34th Street
New York, NY 10001

Dr. Andrew P. Dobson
Department of Ecology and Evolutionary Biology
Eno Hall
Princeton University
Princeton, NJ 08544-1003

Dr. Esteban Domingo
Centro de Biología Molecular Severo Ochoa
Universidad Autonoma de Madrid
Cantoblanco, 28049-Madrid, Spain

Dr. Michael R. Farzan
Department of Microbiology and Molecular Genetics
New England Primate Research Center
Harvard University Medical School
1 Pine Hill Road, P.O. Box 9102
Cambridge, MA 02138

Prof. Neil M. Ferguson
Professor of Mathematical Biology
Mathematical Biology Department
Department of Infectious Disease Epidemiology
Medicine Building, Medical School Campus, St Mary's Campus
Imperial College
London, UK

Dr. Edward C. Holmes
Professor in Biology
The Center for Infectious Disease Dynamics
Pennsylvania State University
326 Mueller Laboratory
University Park, PA 16802

Dr. Kathryn V. Holmes
Department of Microbiology
University of Colorado Health Sciences Center
Aurora, CO 80045

Dr. Yoshihiro Kawaoka
Department of Pathobiological Sciences
School of Veterinary Medicine
University of Wisconsin-Madison
2015 Linden Drive West
Madison, WI   53706

Dr. Lonnie King
Dean, College of Veterinary Medicine
Michigan State University
G100 Veterinary Medical Center
East Lansing, MI 48824-1314

Dr. James S. Koopman
Professor of Epidemiology
Department of Epidemiology SPH
University of Michigan School of Public Health
611 Church Street, Room 203
Ann Arbor, MI 48109-3028

Scott P. Layne, M.D.
Associate Professor
UCLA School of Public Health
Department of Epidemiology
P.O. Box 951772, 71-235 CHS
Los Angeles, CA 90095-1772

Dr. Grant McFadden
Department of Microbiology and Immunology
University of Western Ontario and
Bio Therapeutics Research Group
Robarts Research Institute
Siebens-Drake Building, Room 116.1
1400 Western Road
London, ON Canada N6G 2V4

Dr. X.J. Meng
Associate Professor of Molecular Virology
Center for Molecular Medicine and Infectious Diseases
Department of Biomedical Sciences and Pathobiology
College of Veterinary Medicine
Virginia Polytechnic Institute and State University
1410 Price’s Fork Road
Blacksburg, VA 24061-0342

Dr. Stephen S. Morse
Associate Professor
Department of Epidemiology
Columbia University
Mail: MSPH/ Epi
722 West 168th Street, MSPH 522
New York, NY 10032

Dr. Albert Osterhaus
The National Influenza Centre and Department of Virology
Erasmus Medical Centre Rotterdam
Dr Molewaterplein 50
3015 GE Rotterdam
The Netherlands

Dr. Mark A. Pallansch
Respiratory and Enteric Viruses Branch
Division of Viral and Rickettsial Diseases
National Center for Infectious Diseases
Centers for Disease Control and Prevention
1600 Clifton Road NE, Mailstop G-17
Atlanta, GA 30333

Dr. Colin R. Parrish
Professor of Virology
Baker Institute for Animal Health
College of Veterinary Medicine
Cornell University
Ithaca, NY 14853

Dr. John T. Patton
Senior Investigator
Division of Intramural Research (DIR)
NIAID, NIH
Bethesda, MD 20892

Dr. Daniel R. Perez
Assistant Professor
Department of Veterinary Medicine
University of Maryland
Room 1215, 8075 Greenmead Drive
Avrum Gudelsky Building
College Park, MD 20742

Clarence J. Peters, M.D.
Director for Biodefense
Center for Biodefense and Emerging Infectious Diseases
The University of Texas Medical Branch
301 University Boulevard
Galveston, Texas 77555

Dr. Linda J. Saif
Food Animal Health Research Program
Ohio Agricultural Research and Development Center
The Ohio State University
1680 Madison Avenue
Wooster, OH 44691

Dr. Liisa Selin
Department of Pathology
University of Massachusetts Medical School
55 Lake Avenue North
Worcester, MA 01655

Dr. Jeffery Taubenberger
Armed Forces Institute of Pathology, AFIP Annex
Department of Molecular Pathology
Building 101, Room 1057D
1413 Research Boulevard
Rockville, MD 20850

Dr. Marc Van Regenmortel
Biotechnology School of the University of Strasbourg
Ecole Superieure de Biotechnologie de Strasbourg
Centre National de la Recherche Scientifique (CNRS)
Strasbourg, France

Dr. Luis P. Villarreal
Professor, Molecular Biology & Biochemistry
School of Biological Sciences
Director, Center for Virus Research
Director, Viral Vector Facility
School of Biological Sciences
University of California-Irvine
3232 McGaugh Hall, Mail Code 3900
Irvine, CA 92697

Dr. Robert G. Webster
Department of Infectious Diseases
St. Jude Children’s Research Hospital
332 North Lauderdale
Memphis, TN 38105-2794

Dr. J. Lindsay Whitton
Department of Neuropharmacology
The Scripps Research Institute
La Jolla, CA 92037

Dr. Mark Woolhouse
Chair of Veterinary Public Health and Quantitative Epidemiology
Centre for Tropical Veterinary Medicine
University of Edinburgh, UK

Dr. Hu Zhihong
General Director, Wuhan Institute of Virology, Chinese Academy of Sciences
Joint Laboratory of Invertebrate Pathology and Key Laboratory of Molecular Virology
Wuhan Institute of Virology
Chinese Academy of Sciences
Wuhan, People's Republic of China


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Summary

The overall goal of the workshop was to consider the topic of viruses that could emerge and become widespread in the human population through host switching and the special issues that are raised by that type of viral emergence. The specific objectives were:

(1) To consider how such emergences have occurred in the past and the principles that can be learned from those examples.

(2) To understand the sources of new viruses and, for zoonoses, the nature of their reservoirs; to consider the changes in reservoir-human interactions and how those impact on the emergence of new viruses in humans.

(3) To examine the molecular controls of viral host range and the number of separate molecular barriers involved and to consider how viruses cross such barriers.

(4) To define the evolutionary mechanisms and pathways that allow viruses to gain the necessary changes, under the right circumstances, to transfer and infect new hosts.

(5) To consider how viruses might enter human populations in the future and whether those types of emergences can be predicted.

(6) To consider how those might be prevented, or if they do occur, how they might be controlled. Control strategies to be considered include those implemented early in the outbreak or others that would minimize the harm done if a virus does get away.

The idea of the meeting was to define the broad principles of these topics in a way that would help the virological and public health communities to understand these types of emergence and to use the information to plan for the future. A manuscript that reports the findings and conclusions of the workshop for publication is under development.

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Last Reviewed: February 13, 2006
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