Influenza, typically referred to as the flu, is a viral disease that has been around for
a long time.
Descriptions of local outbreaks of what’s believed to be influenza date back to ancient times.
However, the most famous influenza pandemic swept the world back between 1918 and 1919.
Even though this pandemic is commonly known as the “Spanish Flu,” this name is actually
the result of widespread misunderstanding, and experts can’t agree on precisely where
it came from.
What we do know is that about one-third of the world’s population became infected with
this virus, and it’s estimated that at least 50 million people died worldwide.
Let’s dig into the details of the virus on the molecular level.
All influenza is caused by one of three influenza viruses: A, B, or C, which belong to the virus
Family Orthomyxoviridae.
In fact, Influenza A, B, and C viruses are the only members of the Orthomyxoviridae family.
Since Influenza A causes the most serious disease, we’ll focus on the details of that
one here.
Influenza viruses themselves can be spherical or tubular in shape, ranging in diameter from
80 to 120 nanometers or so.
Influenza A has eight segments of single-stranded RNA, which are enclosed in a protein capsid.
The capsid is surrounded by a lipoprotein envelope that it gets from the host cell membrane
during the maturation step of replication, and that lipoprotein has glycoprotein spikes
poking out all around.
The two glycoproteins that make up the spikes of the envelope are called hemagglutinin,
abbreviated with the letetr H, and neuraminidase, abbreviated with the letter N. The spikes
are an important part of the virus’ ability to cause damage, so we should try to understand
why this is the case.
The hemagglutinin spikes allow the virus to recognize and then attach to specific receptors
on host epithelial cells.
Viruses that have these hemagglutinin spikes also cause red blood cells to stick together,
which is called hemagglutination, and this is one method for identifying if a virus is
present.
Neuraminidase is an enzyme that’s crucial for releasing newly formed virions from the
host cell.
Influenza viruses bud out of the host cell, taking some of the host’s lipoprotein envelope
with it, but the newly formed virions need neuraminidase to break free from the surface
receptors they were bound to.
Neuraminidase destroys these receptors so that the virus can go on to infect another cell.
And while we’re talking about this mechanism, anti-influenza drugs like Tamiflu act by inhibiting
neuraminidase activity, which is why it’s important for these drugs to be taken very
early in the infection cycle.
You’ve likely heard people talk about “H1N1” or “H5N1” influenza viruses, but what
does that actually mean?
Influenza A viruses can be split into subtypes based on what kinds of hemagglutinin and neuraminidase
spikes they have.
These subtypes are given numbers, so H1, H2, N1, N2, and so on.
There are 16 H and 9 N subtypes total, but only H1, H2, and H3, as well as N1 and N2,
are spread amongst humans.
The “avian flu” that got passed around back in 1997 was caused by influenza virus
H5N1, while the “swine flu” epidemic of 2009 was caused by influenza virus H1N1.
Influenza typically enters a host by inhaling aerosolized respiratory secretions.
So basically, little sneeze or cough droplets, from a person who has the flu.
However, you can also pick up the flu virus from commonly-touched surfaces such as doorknobs
or household items.
In this case, the person touches something with the virus on it and then accidentally
touches their face, transferring the virus into the mucous membranes of the face via
the nose or eyes.
The virus then attaches, using its hemagglutinin spikes, to respiratory epithelial cells coated
in cilia, and uses the process of endocytosis to enter the cell.
From there, the virus replicates its RNA and builds more of its own proteins using the
host cell’s machinery.
Within six hours, mature virions bud out of the host cell, taking some of the host cell’s
membrane with them, and the virus then can spread rapidly to nearby cells.
In most cases, a small percentage of people with influenza die, but when outbreaks are
widespread, that means the number of people who are likely to die goes up.
And actually, most of the deaths that occur from influenza outbreaks are from secondary
bacterial infections like pneumonia.
Epidemics of influenza happen each year, but global pandemics only pop up periodically.
The reason for this really boils down to the mutation and evolution of the virus.
First, there’s the concept of antigenic drift, which is important for Influenza A
and B viruses.
Basically, point mutations in the genes that encode the hemagglutinin and neuraminidase
spikes, causing a single amino acid discrepancy during normal viral replication, for instance,
can grant the virus the ability to escape the immune system.
In other words, one single mutation might weaken the interaction of the virus with antibodies
that we’ve already made against them.
Antigenic drift commonly occurs during the course of a standard flu season.
In some cases, enough changes accumulate in a virus that a new subtype evolves.
A more uncommon occurrence is the idea of antigenic shift.
Only influenza A viruses can do this, because it requires swapping of genetic material between
different subtypes of the same kind of virus.
Remember when we talked about the genome of the influenza virus being segmented, meaning
that viral proteins are encoded on eight separate segments?
If someone is infected with two different subtypes of Influenza A at the same time,
so that both viruses are replicating within the same cell, it’s possible for a newly
created virus to contain pieces of each of the subtypes.
While this is rare, it’s absolutely possible, and this is the way that viruses are able
to “jump” to infecting new species.
This viral genome reassortment is what causes pandemic influenza.
Now let’s talk about treatment and prevention.
Since influenza is a virus, antibiotics don’t work to treat infection.
Some antiviral medications can prevent disease if taken early, but the main form of prevention
is by vaccine.
Since these viruses are prone to continual evolution, it is very difficult to create
a vaccine that offers lifelong immunity.
Because of antigenic drift, a slightly new strain of influenza is always emerging, and
it typically takes between 6 and 9 months to manufacture large quantities of a vaccine
once a new strain emerges.
However, scientists are working to develop a universal flu vaccine that could revolutionize
influenza prevention, which would neutralize a major killer worldwide.