Pigs, poultry, and pandemic influenza: how zoonotic pathogens threaten human health

Abstract

Emerging infections have an enormous impact on human health, food supply, economics, and the environment. Animals, and wild animals in particular, are considered to be the source of more than 70% of all emerging infections in humans. Two zoonotic influenza viruses that successfully spread from animals to humans are highly pathogenic avian influenza (HPAI) H5N1 virus, originating from poultry, and pandemic H1N1 influenza (pH1N1) virus, thought to originate from domestic swine. In this review, we discuss our research on the host species barrier for these viruses, concentrating on three questions: how does HPAI H5N1 virus transmit from birds to humans; what are the within-host dynamics of HPAI H5N1 virus and pH1N1 virus in humans and other mammals; and what determines transmission of influenza viruses among humans. To contain and eradicate zoonotic influenza viruses requires not only strategic virus surveillance of both animal and human populations, but also a better understanding of the hurdles that such a virus needs to jump over in order to cross the species barrier and cause a human pandemic. Advances in these two areas will allow us to better predict the risk of emergence of zoonotic influenza viruses in the human population.

Fig. 1

Schematic illustrating phases in overcoming species barriers. (a) Interspecies host-host contact must allow transmission of virus from donor species to recipient species. (b) Virus-host interactions within an individual of recipient species affect the likelihood of the virus replicating and being shed sufficiently to infect another individual of recipient species. (c) Intraspecies host-host contact in recipient species must allow viral spread (R₀  >  1) in the presence of any pre-existing immunity. Superspreader events (red asterisk) early in the transmission chain can help this process. (d) The pathogen must persist in the recipient species population even during epidemic troughs (after most susceptible individuals have had the disease) so that subsequent epidemics can be seeded: If few susceptibles are left, the virus may (stochastically) go extinct in epidemic troughs. Viral variation and evolution can aid invasion and persistence, particularly by affecting host-virus interactions. Reprinted from Science [3] with permission from the American Association for the Advancement of Science

Fig. 2

Schematic representation of known events involving cross-species transmission of avian influenza viruses to mammals besides humans. Cross-species transmission of avian influenza viruses to swine, horses, harbour seals, whales and mink. The source of infection is not precisely known but is thought to be wild bird reservoirs (Anseriformes, such as ducks, and Charadriiformes, such as gulls). Poultry can become infected with avian influenza viruses and may transmit the viruses to swine and horses, when reared together. Horses have transmitted equine influenza H3N8 virus to domestic dogs. Reprinted from Scientific and Technical Review [11] with permission from the World Organisation for Animal Health (OIE)

Fig. 3

Attachment of human (H3N2 and H1N1) and avian (highly pathogenic H5N1) influenza viruses in human lower respiratory tract. Reprinted from American Journal of Pathology [8] with permission from the American Society for Investigative Pathology

Fig. 4

Cats infected with influenza A virus (H5N1) have lesions associated with virus replication in multiple tissues, including brain and heart. Necrotizing and inflammatory changes are seen (left column). Serial sections of these tissues (right column) show that these lesions are closely associated with the expression of influenza virus antigen. Tissues were stained either with hematoxylin and eosin (left column) or by immunohistochemistry using a monoclonal antibody against the nucleoprotein of influenza A virus as a primary antibody (right column). Reprinted from American Journal of Pathology [13] with permission from the American Society for Investigative Pathology

Fig. 5

Histological and immunohistochemical scoring in the lungs of ferrets inoculated with different influenza viruses. Histological scoring of samples stained with hematoxylin and eosin (HE) showed that the alveolar lesions in the new H1N1 virus (synonym for pH1N1 virus) group were intermediate in severity between those of the seasonal H1N1 virus group and the highly pathogenic avian influenza (HPAI) H5N1 virus group, and that the bronchiolar lesions in the new H1N1 virus group were the most severe of all three groups. Scoring of the immunohistochemical analysis (IHC) showed that influenza virus antigen expression in the new H1N1 virus group was high in alveoli, bronchioles, and bronchi. In the HPAI H5N1 virus group, the scores were highest for alveoli and lower in bronchioles and bronchi. In the seasonal H1N1 virus group, scores were low at all three levels. Reprinted from Journal of Infectious Diseases [16] with permission from Oxford University Press

Fig. 6

Attachment of pandemic influenza H1N1 virus (upper panel) and highly pathogenic avian influenza H5N1 virus (lower panel) to ciliated epithelial cells in the human upper respiratory tract. Reprinted from American Journal of Pathology [24] with permission from the American Society for Investigative Pathology