HOW IT WORKS
When you read or listen to news about the bird flu, you might hear about the spread of H5N1, the mad dash to buy Tamiflu, or the warnings of a pandemic. However, one thing that is overlooked often is the virus's mechanics. In other words, how does it work?
Anatomy of a virus
If you were to look at an influenza virus through a microscope, it would look like a sphere with many spikes and mushroom shaped objects on its surface. The exterior of the virus is composed of a lipid (fat) envelope covered with two types of protein molecules called surface antigens. The spikes are known as hemagglutinin (HA) and the mushrooms are known as neuraminidase (NA). Each hemagglutinin spike is made up of three entwined molecules while each neuraminidase mushroom is comprised of four entwined molecules. Also on the surface of the virus are M2 proteins, which allow the virus to adjust its interior acidity. Inside the lipid envelope, there are eight RNA gene segments called RNPs (RNA molecule+ Nucleoprotein+ Polymerases). Finally, there are the ball shaped M1 proteins, which act as cushions for the RNPs inside.
A CLOSER LOOK: What's in a name?
H5N1, H1N1, H3N2... the flu virus designations are interesting and puzzling. But how do scientists come up with these strange names. According to experts, there are 15 different types of hemagglutinin molecules and 9 different types of neuraminidase molecules. Virologists identify Influenza A viruses by their specific hemagglutinin and neuraminidase molecules. In 1980, scientists adopted a general formula for naming Influenza A viruses, HxNy (x represents the type of hemagglutinin molecule and y represents the type of neuraminidase molecule.)
For example, an avian flu virus with hemagglutinin molecule 3 and neuraminidase molecule 2, its name would be H3N2.
How influenza replicates
The process of cell replication can be explained in three phases: initiation, replication, and release.
Initiation
During initiation, the hemagglutinin (HA) spikes bind to the surface of a cell. After binding, the virus is enveloped by a capsule made from the cell's membrane, which then breaks off from the surface and goes into the cell. This process is known as endocytosis. After entering the cell, the virus's M2 protein pumps ions into the capsule, to make it more acidic. When the capsule becomes acidic enough, the virus will merge with the capsule. Eventually, a hole is formed and the RNPs leave the capsule, heading straight for the cell's nucleus, where replication begins.
Replication
The RNPs enter the nucleus, where new viral RNA and proteins will be produced. Inside the nucleus, the virus's genetic blueprint (known as vRNA) produces messenger RNA (mRNA) and direct copies of its genetic material (cRNA). The mRNA 'oversees' the making of various proteins, while the cRNA is used to make additional copies of the virus's genetic material. Hemagglutinin, neuraminidase, and M1 proteins form on the outside of the cell membrane, while newly made nucleoproteins combine with vRNA to form nucleocapsids, another name for the RNPs. With everything in place, the release phase begins.
Release
During the final phase, the nucleocapsids are assembled and the new virus particles begin to take shape. After assembly, the viruses are released from the cell, in a process known as budding. New virus particles are gradually released from the cell for several hours until the cell eventually dies off. The new viruses then attach themselves to new cells, starting the process of replication again.
Three essential facts
- RNA is extremely error prone: on average, each new virus differs from its parent by at least one nucleotide.
- Influenza is the only virus that undergoes true antigenic drift (genetic changes in the virus that occur because of errors in replication.)
- Two different viruses can infect a cell at the same time. For instance, if human and an avian flu virus infect a pig cell, they can swap genes. This swap results in a new flu subtype that has both avian and human flu characteristics. This 'reassortment' is known as antigenic shift.