When the infection stays restricted to this region of the respiratory tract, it causes rather mild disease. Upon entering a new host, IV establishes infection in the epithelial cells lining the upper airways 7.
The viral protein hemagglutinin (HA) of human IV binds preferentially α2,6-linked sialic acid (Sia) moieties located on the surface of the host cell, thus triggering viral entry through clathrin-mediated endocytosis 6. Influenza virus (IV) is enveloped, with a negative single strand RNA genome. Lastly, when the reassortant viruses possess new virulence factors, they can be associated with increased pathogenicity. This process, when accompanied by the expression of new surface glycoproteins, is named antigenic shift, as it results in the emergence of strains that infect immunologically naive humans and cause potentially pandemic outbreaks 5. The arrangement of the viral genome on multiple RNA segments allows for the exchange of genetic material between different viral strains which co-infect the same host, giving rise to novel gene-reassorted variants. In addition, due to their ability to cross the species barrier, IAVs pose a high pandemic risk. As a consequence, seasonal epidemics endanger every year children, elderly people, pregnant women, and people of any age with comorbid illnesses 4. In a process called antigenic drift, IAVs rapidly acquire adaptive mutations allowing them not only to evade the host immune response but also to neutralize annual attempts to generate effective vaccines 3. Although the latter are almost exclusively found in the human population, IAVs emerge from a huge zoonotic reservoir 2. Influenza is caused, in humans, by influenza A (IAV) and influenza B (IBV) viruses.
More than a century after the Spanish pandemic, the health systems are still struggling to cope with seasonal influenza, something that bodes poorly in the event of a novel pandemic. Influenza is a highly contagious respiratory infection that accounts every year for about ~3–5 million cases of severe illness and up to 650,000 deaths 1.
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