Influenza Virus: Flu, Genetic Drift & Shift, Neuraminidase & Hemagglutinin


Distinguished future physicians welcome to
Stomp on Step 1 the only free videos series that helps you study more efficiently by focusing
on the highest yield material. I’m Brian McDaniel and I will be your guide on this
journey through the Flu. This is the 6th video in my playlist covering microbio and we are
going to review the influenza virus as well as viral genetics such as reassortment, genetic
drift & genetic shift. Influenza Virus causes the Flu. Influenza
should not be confused with the bacteria Haemophilus influenza (AKA H Flu). The influenza virus
causes a very common acute respiratory tract infection. Clinically it presents as fatigue,
rhinorrhea (runny nose), myalgia (muscle pain), fever, cough/sore throat, and headache. There
are laboratory tests available, but the flu is almost always a clinical diagnosis. It
is spread mainly through air via respiratory droplets. Symptoms usually begin a couple
days after being infected, but some patients remain asymptomatic. Most symptomatic patients
will recover completely within 1 to 2 weeks. Sometimes it is difficult to tell the difference
between the flu and the common cold which is caused by a different virus. There is a
lot of overlap in symptoms between the two, but the flu is usually more severe and lasts
longer. A high fever and body aches are also more often associated with the flu. Question stems usually mention the time of
year as a majority of flu cases within the US occur during between November and April.
There is not a definitive answer as to why the flu occurs in the winter, but it could
just be due to people being indoors and in close proximity more often. Other potential
contributing factors include increased travel during the holidays and drier air. The question
stem may also give you a big clue by mentioning that the patient is unvaccinated or that they
had a recent sick contact. Usually, the flu is self-limited and only
supportive treatment with over the counter medications is needed. Antiviral treatment
is recommended for patients at high risk of complications. It should be started within
the first 2 days of symptom onset. Antiviral options include neuraminidase inhibitors such
as Oseltamivir (trade name Tamiflu) & Zanamivir. The general public thinks of the flu as a
relatively mild infection. However, serious complications and even death are possible
especially in high risk populations. There are hundreds of thousands of deaths worldwide
attributed to the flu each year. The infection can spread into the lower respiratory tract
and cause viral pneumonia or weaken the immune system leading to a secondary bacterial infection
(AKA “superinfection”). Children, pregnant women, and the elderly have a higher risk
for complications. Patients with a history of smoking, COPD, Asthma, immunosuppression,
and other health conditions also have increased risk. There is of course a yearly Influenza Vaccine
(AKA Flu Shot) that you should be very familiar with. As medical personnel you are probably
required to get it every year by your school or healthcare organization.
The vaccine is recommended for nearly everyone, but is especially important in high risk individuals.
It is available in inactivated and live attenuated forms.
Since it takes a lot of time to make millions of vaccines, predictions have to be made in
advance about what strains of the virus will be most common. Unfortunately, sometimes these
predictions end up being partially wrong. This is why in certain years the vaccine isn’t
as effective as others. Even in the best of years the vaccine isn’t
100% effective as there is a lot of variety among influenza viruses. This is one of the
reasons some patients believe “the flu vaccine doesn’t work.”
Even worse there is widespread belief that “you can get the flu from the flu vaccine”
which is highly unlikely. Part of this belief may be related to the fact that it takes a
couple weeks after getting the vaccine for it to “kick in.” Therefore, some people
will get the infection before the vaccine starts working and claim the vaccine doesn’t
work. Alternatively patients may get another virus,
such as the common cold, after getting the vaccine and mistakenly think they got the
flu. Some patients also have a mild reaction after
receiving the vaccine that includes mild flu like symptoms. This mild reaction may mistakenly
be understood as an infection and a failure of the vaccine.
More serious allergic reactions are possible and the vaccine is contraindicated in those
with severe egg allergy. Here is the table we keep referencing during
our virus videos. You can see that Influenza virus is enveloped with a lipid outer layer The virus also has a single stranded RNA genome. Interestingly the RNA is split into about
8 separate segments similar to the Rotavirus. The segmented nature of these genomes allows
for RNA segments to be exchanged between viruses, a process known as Reassortment. In this case
2 different influenza viruses infect a single host and a mixture of their genome segments
can create a new virus with much higher virulence. The sudden change in the virus genome caused
by reassortment is called Genetic Shift and is responsible for pandemics (or global disease
outbreaks). Typically this involves a human strain of the virus gaining a completely new
surface antigen from a strain of the virus which typically resides in another species.
This new surface antigen means that the human immune system can no longer detect the virus
based on “experience” gained from previous encounters with the influenza virus. A recent
example includes the “Swine Flu” pandemic which was caused by a combination of genomes
from pig and human strains of the virus. There is also a more gradual process for the
influenza virus to adapt called Genetic Drift. In this process mutations slowly accumulate
in the viral genome. This leads to an increasing diversity within the virus. In particular
mutations that affect the surface antigens of the virus are important. Some of these
mutations will give the virus a survival advantage that allows it to cause epidemics (AKA the
seasonal flu outbreaks that are mostly restricted to individual countries). However, since the
new version of the virus still resembles strains from previous epidemics part of the population
remains immune. Here is a table to summarize the difference
between genetic drift and genetic shift. Shift is caused by reassortment of the segmented
viral genome often across multiple species. The change is sudden. It results in the virus
gaining a completely new surface antigen so nearly everyone is susceptible to the virus.
It can lead to yearly epidemics or worldwide pandemics. It is present in Influenza type
A which is the type of influenza present in multiple different species. Rotavirus, which
also has a segmented genome, can have genetic shift too. Genetic drift is the accumulation of random
mutations that slowly leads to a surface antigen that is slightly different than subtypes of
the virus that caused the years previous epidemic. Drift generally doesn’t cause pandemics
and leads to less serious yearly epidemics as some of the individuals in the population
remain immune since this new type of the virus looks similar to subtypes present in the population
the previous year. Genetic drift is present in Influenza A, B & the rarer Type C as well
as many different species of virus. This table is available on my website. Hemagglutinin (HA) and neuraminidase (NA)
are glycoproteins on the outside of the Influenza virus envelope.
You can see HA here in yellow and NA here in red. The picture also shows the segmented
RNA genome. Hemagglutinin is important for the virus to
be able to bind to target cells and insert its viral genome. Neuraminidase is important
during the process of the virus releasing offspring from the infected cell.
There are many subtypes of hemagglutinin and neuraminidase, but only H1 through H3 and
N1 & N2 are found commonly in humans. You have likely heard of subtypes of the Influenza
A virus such as H1N1 which includes hemagglutinin 1 and neuraminidase 1.
This is the subtype of the virus that caused the Spanish Flu pandemic in 1918 and the Swine
Flu pandemic in 2009. Alternatively, Influenza Type A subtype H5N1,
more commonly referred to as “Bird Flu,” was the center of media attention in 2008.
You don’t need to know the history of these subtypes for the exam, but I included them
in case you find that interesting. Since HA & NA are so integral to the function
of the virus, they are targets for preventing and treating influenza. The body creates antibodies against Hemagluttinin.
These antibodies bind to HA thereby inhibiting the attachment of the virus to the surface
of host cells. Individuals with antibodies against certain types of HA are immune to
that subtype of the virus. Neuraminidase Inhibitors are a class of antiviral
drugs that prevent the release of viruses by inhibiting the action of the neuraminidase
enzyme. Examples include Zanamivir & Oseltamivir (Tamiflu). If the patient is diagnosed within
48 hours of the onset of symptoms one of these medications can be added to the treatment
regimen to lessen the severity and decrease complications. However, antipyretics and analgesia
are usually sufficient for treatment. That brings us to the end of our video. I
want to send a big thanks to Julia Esparza from Shreveport who’s donation on StomponStep1.com
helped fund this video. If you enjoyed this video and want to make
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