Influenza is an illness caused by viruses from the Orthomyxoviridae family. These viruses are composed of a protein-studded coat that surrounds a genome made up of seven or eight single-stranded RNA segments.
Of the three influenza viruses – which are classified by their structural proteins as types A, B, or C – influenza A causes the most serious and widespread human epidemics and pandemics.
Two proteins (hemagglutinin and neuraminidase) in the coat of the influenza A virus allow it to infect cells and, once the virus has replicated, to break out and spread to other cells. (The Merck Manual, 18th Edition. Influenza. 2006:1595-99)
How Hemagglutinin and Neuraminidase Work
- Hemagglutinin (H or HA) is a glycoprotein on the viral coat that binds to sialic acid receptors in the membranes of cells that line the host’s respiratory tract. After H binds to these receptors, the viral and cellular membranes fuse, and the virus is taken into the cell along with a small envelope of cellular membrane.
- Once inside the cell, the viral genome escapes from its covering, migrates to the cell’s nucleus, crosses the nuclear membrane, and “hijacks” the host cell’s machinery to make copies of itself. Additional copies of H, N, and viral matrix proteins are made as well.
- These manufactured viral components migrate back to the cell membrane where they bud out from the cell, taking a wrapping of cellular membrane for their new coats. However, the new viral coats still contain sialic acid receptors from the host cell. These cellular receptors will bind with viral H proteins and prevent the viruses from exiting.
- It is the task of neuraminidase (N or NA) to enzymatically cleave the sialic acid receptors, thus allowing the virus to break free from the host cell. The virus is now able to bind to another respiratory cell and begin the process anew.
- In essence, the H protein allows the influenza virus to enter a cell; the N protein allows it to escape.
- Infected cells die because they can no longer perform their usual functions or because the virus actually triggers a "suicide switch" within the cell.
Mutations in Influenza Viruses
- Exposure to influenza results in antibody production that generates immunity to re-infection. Changes in H and N proteins result in a decrease in immunity that was conferred by exposure to previously existing strains.
- Since influenza viruses were first recognized as a cause of illness in animals, sixteen H and nine N proteins have been identified. These different proteins are the result of minor mutations (antigenic drift) or major changes (antigenic shift) in the proteins’ structures.
- Antigenic drift usually results in influenza strains that bear some similarity to past strains; therefore, partial population immunity exists, and major outbreaks are unlikely. Conversely, antigenic shift can produce novel strains to which the population has no immunity.
- Genetic reassortment may occur when two different strains infect the same cell (influenza is a “sloppy” virus, in that one strain can easily incorporate genetic material from another strain). This is a not uncommon mechanism for the development of new influenza strains, since there can be several strains circulating among commingling species of flu-susceptible animals.
- Animals that are easily infected by different strains of influenza become “mixing vessels” for the development of novel strains.
When novel influenza strains emerge—historically about three times every century—large-scale epidemics or pandemics occur; depending on the virulence of the virus, the number of fatalities can be striking.
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