Ways in which seasonal and pandemic influenza infections differ

In commenting on another article in the American Journal of Pathology but Gao et al, Kevin Hartshorn nicely summarizes some of the possible reasons why a pandemic influenza kills otherwise healthy young adults more often than a seasonal influenza does. 

The answer is as complex as the milieu of interactions between viral proteins and nucleic acids and our innate and adaptive immune systems, our health, genetic factors, environmental factors and our prior exposure to different influenza viruses - and that's pretty complex!

Hartshorn categorizes the differences between seasonal and emerging influenza impact in young adults using 3 sections:

1. Differences in their ability to cause disease (pathogenicity).
• pandemic influenza generally kill more young adults whereas seasonal influenza kills mostly the elderly and the young
• This is also apparent in ferret animal models
• The viral haemagglutin (HA) protein is key to pathogenesis, playing a central role in pathology due to immune responses and inflammation whereas increases in viral replication are due to the viral replication complex (including PB1, PB2 and PA). Glycosylation of HA is a key pathogenicity determinant because a lack of apical glycosylation allows viral escape from a major non-specific defence; the action of surfacant protein D.
2. Differences in the way the infected host responds to them.
• Pregnant mice and humans show increased severity of disease. This may relate to a reduced innate immune response to pandemic influenza. Bypassing innate immunity may also allow the virus to bypass a key regulatory process, leading to a more over-reactive inflammation.
3. Differences in past history of influenza virus exposures
• Possibly, even with a strong immune cell response, the absence of any prior exposure to a related influenza results in the absence of any cross-protective neutralizing antibodies - the type that can moderate disease - in younger adults compared to older adults. The elderly may have such antibodies from exposures to other H1N1 strains between 1918 and 1957.