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

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.

[1]  R. Webster,et al.  Human influenza A H5N1 virus related to a highly pathogenic avian influenza virus , 1998, The Lancet.

[2]  N. Cox,et al.  Characterization of an avian influenza A (H5N1) virus isolated from a child with a fatal respiratory illness. , 1998, Science.

[3]  I. Brown,et al.  Antigenic and genetic analyses of H1N1 influenza A viruses from European pigs. , 1997, The Journal of general virology.

[4]  R. Webster,et al.  Receptor specificity in human, avian, and equine H2 and H3 influenza virus isolates. , 1994, Virology.

[5]  R. Webster,et al.  Infection of children with avian-human reassortant influenza virus from pigs in Europe. , 1994, Virology.

[6]  R. Webster,et al.  Potential for transmission of avian influenza viruses to pigs. , 1994, The Journal of general virology.

[7]  A. Cooley,et al.  Antigenic and genetic analysis of a recently isolated H1N1 swine influenza virus. , 1993, American journal of veterinary research.

[8]  R. Webster,et al.  Influence of host cell-mediated variation on the international surveillance of influenza A (H3N2) viruses. , 1993, Virology.

[9]  J. Paulson,et al.  Influenza virus strains selectively recognize sialyloligosaccharides on human respiratory epithelium; the role of the host cell in selection of hemagglutinin receptor specificity. , 1993, Virus research.

[10]  R. Webster,et al.  Genetic reassortment between avian and human influenza A viruses in Italian pigs. , 1993, Virology.

[11]  R. Webster,et al.  Characterization of a new avian-like influenza A virus from horses in China. , 1992, Virology.

[12]  W. Fitch,et al.  Evolution of pig influenza viruses. , 1991, Virology.

[13]  W. J. Bean,et al.  Evolution of influenza A virus nucleoprotein genes: implications for the origins of H1N1 human and classical swine viruses , 1991, Journal of virology.

[14]  G. N. Rogers,et al.  Receptor binding properties of human and animal H1 influenza virus isolates. , 1989, Virology.

[15]  R. Webster,et al.  Avian-to-human transmission of the PB1 gene of influenza A viruses in the 1957 and 1968 pandemics , 1989, Journal of virology.

[16]  S. Cusack,et al.  Structure of the influenza virus haemagglutinin complexed with its receptor, sialic acid , 1988, Nature.

[17]  R. Webster,et al.  Sequence requirements for cleavage activation of influenza virus hemagglutinin expressed in mammalian cells. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[18]  N. Saitou,et al.  Polymorphism and evolution of influenza A virus genes. , 1986, Molecular biology and evolution.

[19]  C. Scholtissek,et al.  The nucleoprotein as a possible major factor in determining host specificity of influenza H3N2 viruses. , 1985, Virology.

[20]  J. Paulson,et al.  Influenza virus hemagglutinins differentiate between receptor determinants bearing N-acetyl-, N-glycollyl-, and N,O-diacetylneuraminic acids. , 1985, Virology.

[21]  C. Naeve,et al.  Is virulence of H5N2 influenza viruses in chickens associated with loss of carbohydrate from the hemagglutinin? , 1984, Virology.

[22]  S. I. Golovin,et al.  [Synthesis of a full-length DNA copy of the hemagglutinin gene of the the influenza virus A H1N1 subtype, its cloning and primary structure]. , 1984, Bioorganicheskaia khimiia.

[23]  W. J. Bean,et al.  Are seals frequently infected with avian influenza viruses? , 1984, Journal of virology.

[24]  J. Mackenzie,et al.  Antigenic comparisons of swine-influenza-like H1N1 isolates from pigs, birds and humans: an international collaborative study. , 1984, Bulletin of the World Health Organization.

[25]  J. Paulson,et al.  Differential sensitivity of human, avian, and equine influenza A viruses to a glycoprotein inhibitor of infection: selection of receptor specific variants. , 1983, Virology.

[26]  E. D. Kilbourne,et al.  Hemagglutinin of swine influenza virus: a single amino acid change pleiotropically affects viral antigenicity and replication. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[27]  C. Scholtissek,et al.  Genetic relatedness of hemagglutinins of the H1 subtype of influenza A viruses isolated from swine and birds. , 1983, Virology.

[28]  C. Naeve,et al.  Altered tissue tropism of human-avian reassortant influenza viruses. , 1983, Virology.

[29]  J. Paulson,et al.  Receptor determinants of human and animal influenza virus isolates: differences in receptor specificity of the H3 hemagglutinin based on species of origin. , 1983, Virology.

[30]  R. Webster,et al.  Reassortant virus derived from avian and human influenza A viruses is attenuated and immunogenic in monkeys. , 1982, Science.

[31]  W. J. Bean,et al.  Replication of avian influenza A viruses in mammals , 1981, Infection and immunity.

[32]  H. Klenk,et al.  Proteolytic cleavage of influenza virus hemagglutinins: primary structure of the connecting peptide between HA1 and HA2 determines proteolytic cleavability and pathogenicity of Avian influenza viruses. , 1981, Virology.

[33]  S. Fields,et al.  Nucleotide sequence of the haemagglutinin gene of a human influenza virus H1 subtype , 1981, Nature.

[34]  A. Davis,et al.  Complete sequence analysis shows that the hemagglutinins of the H0 and H2 subtypes of human influenza virus are closely related. , 1981, Virology.

[35]  Y. Matsuoka,et al.  Duck influenza lacking evidence of disease signs and immune response , 1980, Infection and immunity.

[36]  H. Klenk,et al.  The structure of the hemagglutinin, a determinant for the pathogenicity of influenza viruses. , 1979, Virology.

[37]  C. Scholtissek,et al.  On the origin of the human influenza virus subtypes H2N2 and H3N2. , 1978, Virology.

[38]  R. Webster,et al.  Studies on the origin of pandemic influenza. 3. Evidence implicating duck and equine influenza viruses as possible progenitors of the Hong Kong strain of human influenza. , 1973, Virology.

[39]  R. Webster,et al.  Studies on the origin of pandemic influenza. I. Antigenic analysis of A 2 influenza viruses isolated before and after the appearance of Hong Kong influenza using antisera to the isolated hemagglutinin subunits. , 1972, Virology.

[40]  W. D. Kundin Hong Kong A-2 Influenza Virus Infection among Swine during a Human Epidemic in Taiwan , 1970, Nature.