Influenza virus evolution, host adaptation, and pandemic formation

Newly emerging or "re-emerging" viral diseases continue to pose significant global public health threats. Prototypic are influenza viruses that are major causes of human respiratory infections and mortality. Influenza viruses can cause zoonotic infections and adapt to humans, leading to sustained transmission and emergence of novel viruses. Mechanisms by which viruses evolve in one host, cause zoonotic infection, and adapt to a new host species remain unelucidated. Here, we review the evolution of influenza A viruses in their reservoir hosts and discuss genetic changes associated with introduction of novel viruses into humans, leading to pandemics and the establishment of seasonal viruses.