Influenza as a model system for studying the cross-species transfer and evolution of the SARS coronavirus

Severe acute respiratory syndrome coronavirus (SARS-CoV) moved into humans from a reservoir species and subsequently caused an epidemic in its new host. We know little about the processes that allowed the cross-species transfer of this previously unknown virus. I discuss what we have learned about the movement of viruses into humans from studies of influenza A, both how it crossed from birds to humans and how it subsequently evolved within the human population. Starting with a brief review of severe acute respiratory syndrome to highlight the kinds of problems we face in learning about this viral disease, I then turn to influenza A, focusing on three topics. First, I present a reanalysis of data used to test the hypothesis that swine served as a 'mixing vessel' or intermediate host in the transmission of avian influenza to humans during the 1918 'Spanish flu' pandemic. Second, I review studies of archived viruses from the three recent influenza pandemics. Third, I discuss current limitations in using molecular data to study the evolution of infectious disease. Although influenza A and SARS-CoV differ in many ways, our knowledge of influenza A may provide important clues about what limits or favours cross-species transfers and subsequent epidemics of newly emerging pathogens.