Molecular Basis for the Generation in Pigs of Influenza A Viruses with Pandemic Potential

Author:

Ito Toshihiro1,Couceiro J. Nelson S. S.2,Kelm Sørge3,Baum Linda G.4,Krauss Scott5,Castrucci Maria R.6,Donatelli Isabella6,Kida Hiroshi1,Paulson James C.7,Webster Robert G.58,Kawaoka Yoshihiro58

Affiliation:

1. Laboratory of Microbiology, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060, Japan1;

2. Departamento de Virologia, Instituto de Microbiologia, UFRJ, Rio de Janeiro, RJ 21941-590, Brazil2;

3. Biochemisches Institut, University of Kiel, 24098 Kiel, Germany3;

4. Department of Pathology and Laboratory Medicine, UCLA School of Medicine, Los Angeles, California 90024-17324;

5. Department of Virology and Molecular Biology, St. Jude Children’s Research Hospital, Memphis, Tennessee 381015;

6. Department of Virology, Istituto Superiore di Sanita, Rome, Italy6;

7. Cytel, Inc., and Department of Chemistry, Scripps Research Institute, La Jolla, California 920377; and

8. Department of Pathology, University of Tennessee, Memphis, Tennessee 381638

Abstract

ABSTRACT Genetic and biologic observations suggest that pigs may serve as “mixing vessels” for the generation of human-avian influenza A virus reassortants, similar to those responsible for the 1957 and 1968 pandemics. Here we demonstrate a structural basis for this hypothesis. Cell surface receptors for both human and avian influenza viruses were identified in the pig trachea, providing a milieu conducive to viral replication and genetic reassortment. Surprisingly, with continued replication, some avian-like swine viruses acquired the ability to recognize human virus receptors, raising the possibility of their direct transmission to human populations. These findings help to explain the emergence of pandemic influenza viruses and support the need for continued surveillance of swine for viruses carrying avian virus genes.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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