How can bird influenza viruses contribute to new influenza A viruses in humans and other mammals?

Bird influenza viruses contribute to the emergence of new influenza A viruses in humans and other mammals primarily through two mechanisms: genetic reassortment and direct transmission followed by adaptation.12

Genetic Reassortment

Influenza A viruses possess an RNA genome organized into eight segments, which allows for a process known as genetic reassortment. This often occurs when an intermediate host, such as a pig, is simultaneously infected with both avian and human influenza viruses. During replication, the viruses can exchange genetic segments, resulting in a new subtype with surface proteins—hemagglutinin and neuraminidase—that are immunologically distinct from those previously circulating in humans. Because the human population lacks immunity to these novel antigens, such reassortment events can trigger pandemics.132

Direct Transmission and Adaptation

New influenza strains can also emerge when avian viruses jump directly to humans or other mammals. In some cases, these viruses may undergo multiple mutations as they adapt to mammalian cells. While some bird flu viruses are highly pathogenic in humans, they often lack the ability to transmit efficiently between people; however, ongoing evolutionary changes continue to pose a risk for the development of pandemic capability.124