Flu is often used for any condition that is associated with symptoms like runny eyes, runny nose, scratchy throat, etc. These symptoms could be the result of allergies or infection with one of many viruses including those known as the influenza virus. Consequently people with these symptoms often assume that they have flu. However, influenza virus infection also results in headache, fatigue, body ache, chills and fever, the last three being more characteristic of influenza.

There are three different influenza viruses, influenza A, influenza B and influenza C. Symptoms caused by all three viruses are almost indistinguishable, although those resulting from influenza A virus are more severe and have relatively higher morbidity and mortality. It is therefore important to ascertain which of the three viruses, if any, are at the root of symptoms. Firstly if they are due to influenza A infection, more public health measures to prevent its spread can be put in place. Secondly, better care of those with high risk of complications can be treated with anti-influenza drugs and thirdly, people at higher risk of getting infected, such as the very young, the elderly and those with conditions that weaken their defense against infection can be immunized.

Influenza A virus has several types, depending on the nature of its surface proteins. Swine flu is caused by one of these types, isolated initially from both pigs and humans simultaneously in 1918. Hence, the ailment cause by this virus type is called the 'swine flu'. The swine flu virus is distinct from other influenza viruses in the composition of some of its proteins. Since its original naming, the virus has caused many seasonal epidemics and pandemics including the current one.

In order to understand the mystery of "H1N1", one has to be familiar with the virus anatomy. Like many other viruses, the influenza virus is a particle with a protein-lipid membrane on the outside. Within the particle, there are genes for 8 different proteins; two of these being hemagglutinin (H) and neuraminidase (N) protrude from the membrane (Figure 1). There are several forms of these proteins which are recognized as H1, H2, H3, etc. and N1, N2, N3, etc. and different influenza A viruses have different H and N combinations. These proteins are very important for the viruses' survival.

Since viruses can survive and grow only inside a living cell, they have to have a way of getting inside the cell where they multiply and then they have to come out to infect other cells in the body. The initial infection of the cell requires the virus to attach itself to the membrane and this is accomplished by the interaction of the H protein with certain sugar containing molecules (neuraminic acid) on the cell. After attachment, the virus is internalized and replicates inside the cell. The mature virus makes it's way out along with the host cell membrane. In order to move on to infect other cells, the virus has to detach itself from the infected cell and attach to another. The detachment process is accomplished by degradation of neuraminic acid by the N protein. Thus, interference with either H and/or N protein will disrupt the attachment of the virus to infect cells and its dissemination to other cells. This disruption is achieved by interaction of specific antibodies (protective proteins) against H and N proteins that are produced by our cells in response to immunization with the flu vaccine. Thus, it is important to get the flu shots (immunized) every year soon after the appearance of the virus in the community.

There are several forms of H and N proteins (H1, H2, H3, etc. and N1, N2, N3, etc.) and different types of influenza A viruses can have different combinations of these H and N proteins. An influenza virus appearing one year may have a different combination of H and N proteins from the previous year. The acquisition of new protein combinations forms is made possible by the exchange of the protein genes between two different influenza viruses within cells of a host, normally a pig, infected with two different types of flu virus. For example, a pig can be infected simultaneously with two virus types, one with H3N1 proteins and another with H1N2 (Figure 2). Since these proteins require different individual genes for their synthesis, there can be intermixing of these genes within the dually infected cell. As a result, these pigs will propagate two different types of influenza A viruses, one bearing H1N1 and the other with H3N2 surface proteins. Either of these could be the cause of an epidemic. Since each H and N form varies in its chemical composition from the others, antibodies against one form do not react well with the other and immunization against a virus with one HN combination will not afford protection against a virus with another HN combination. As a matter of fact the current H1N1 virus is a mosaic of four different types of influenza A viruses: its gene composition is 17% human influenza virus, 18% Eurasian swine flue, 31% classical American swine flu and 34% North American avian flu.

Now, why do we need a new vaccine every year and why does it require several months for it to become available? It is because the HN combination of the emerging influenza virus is not totally predictable and there are frequent mutations in these proteins. Therefore, vaccines against the virus type prevalent in one year will not be effective against virus emerging the following year. Consequently a new vaccine has to be produced at the onset of each flu epidemic. This entails the isolation of the emerging virus, characterization of it in HN form and propagation of large quantities of the virus. The virus has to be inactivated and tested for its safety and effectiveness to produce immunity (antibodies) before it is released for use.

There are several ways to manage an emerging influenza epidemic. There are several drugs that can be used to treat severe cases, especially those who are at risk of complications. These include Aamantadine and Rimantadine that are effective against influenza B and C but are of little value against influenza A. The other two drugs, Oseltamavir (Tamiflu) and Zanamavir (Relenza) are effective against influenza A virus. However, because of their high cost, they should be used judiciously when warranted by a high risk of complications. Also, it is important to administer immunization as soon as an appropriate vaccine is available, following the CDC recommendation for prioritization of population at risk. A good way of keeping influenza virus (and many other viruses) from spreading is for the infected person to stay away from public places and avoid contact with other people.

Abdul Ghaffar, PhD
Professor Emeritus
Department of Pathology Microbiology and Immunology
USC School of Medicine
ghaffar@uscmed.sc.edu

Links:

Swine Flu-Center for Diease Control and Prevention

South Carolina Department of Health

Swine Flu 101 for Senior Citizens