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Influenza virus

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Influenza virus

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Influenza virus

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A team of researchers is attempting to develop a new pharmacotherapy for the treatment of respiratory infections. Pathogen X, as identified by the researchers, is introduced to an in vitro model consisting of human nasopharyngeal epithelial cells grown within a culture container. Pathogen X is found to produce an enzyme that binds sialic acid residues on the surface of nasopharyngeal epithelial cells. This enzyme allows pathogen X to subsequently enter the epithelial cells. Clinically, pathogen X causes symptoms including shortness of breath, fevers, myalgias, and joint pain. Furthermore, infection by pathogen X can predispose patients to subsequent infection by Staphylococcus aureus. Which of the following is the most likely identity of pathogen X?  

Transcript

Content Reviewers:

Rishi Desai, MD, MPH

Contributors:

Tanner Marshall, MS

Influenza, the virus that causes the flu, is one of the most common infectious diseases.

Now, there are three types of influenza that infect humans, called type A, type B, and type C, each one with slightly different genome and proteins.

Influenza belongs to the virus family Orthomyxoviridae - and type A and B have genomes that are made up of eight RNA segments, whereas type C, has a seven-segment RNA genome, with each segment containing a few genes.

Now, type A, the most common type of influenza virus, can be further subdivided based on two of the glycoproteins on its protective envelope surface; H protein, or Hemagglutinin, and N protein, or neuraminidase.

Hemagglutinin and Neuraminidase can vary a bit in their structure, so different versions are identified by a number.

For example, type A subtype H3N2, sometimes just called H3N2, has hemagglutinin number 3 and neuraminidase number 2 on its surface.

H3N2 and H1N1 are the most common type A subtypes to infect humans, but they both also infect various animals.

To give the full name of a virus, we use the type, the original host that it came from, the location where the virus was first identified, which is usually a city, the strain number, the year of origin, and—for type A influenza—the subtype named by the H and N glycoproteins.

For example, an H1N1 type A flu virus of duck origin from the province of Alberta, Canada, that is the 35th strain discovered in 1976 would be called A/duck/Alberta/35/76 (H1N1).

Type B influenza is less common, it only infects humans and doesn't mutate as often as type A.

Type B influenza only has a few types of H and N glycoproteins on its surface.

Therefore the naming pattern is similar to type A influenza without the H and N subtype included at the end or the host type, since it only infects humans.

For example, a type B virus found in Yamagata, Japan, which is the 16th strain discovered in 1988 would be called B/Yamagata/16/88.

Finally, there's type C influenza which is only one species, and is the least common and least likely to mutate of the three.

Influenza C usually causes mild disease in children, and unlike type B, it can affect both humans and pigs.

Rather than hemagglutinin and neuraminidase, type C influenza uses a hemagglutinin-esterase-fusion protein to enter and exit cells.

So, type C influenza is named without the HN subtype, similar to how type B's written.

For example, a type C virus found in Sao Paulo, Brazil which is the 37th strain discovered in 1982 would be called C/Sao Paulo/37/82.

Of the three types, type A is the most common and causes the most severe illness.

One reason is that the virus has a tendency to mutate its H and N glycoproteins during replication, and this allows daughter viruses to form that are slightly different from one another and from the parent virus.

Over time, if enough of these small changes happen, even if somebody's immune to the original virus, the mutated virus may have H and N glycoproteins that are different enough to allow it to evade antibodies, and therefore infect people who were immune to previous strains.

This process is called genetic drift, and is why individuals can get sick from influenza year after year or from two different strains of influenza in the same year.

In addition, a process called antigenic shift, is where sometimes a virus will be circulating among animal populations like pigs or chickens and then will suddenly change in a way that allows the virus to infect humans as well.

This happens when the same cell, let's say a pig cell, gets infected with two similar flu viruses, for example a flu strain that usually infects humans and one that usually infects pigs.

Since the viral genome is in segments of RNA, the pieces might reassort, or mix, allowing new viruses to have a mix of RNA segments in them.

Reassortment results in viruses that have entirely new hemagglutinin, neuraminidase, or both.

When a virus is produced that can infect human cells and has entirely new proteins, people have little or no protection against it, and it can rapidly spread through the population.

This antigenic shift process is responsible for three major influenza pandemics in the 20th century, including the Spanish Flu in 1918, which killed 3 percent of the world's entire population at the time.

The flu is transmitted when an infected person sneezes or coughs, which spreads thousands of droplets containing the virus into the local area, up to about two meters or six feet away.

These droplets can then land in the mouths or noses of people nearby, or get inhaled into the lungs.

The virus can also survive on surfaces for a few hours, so it's possible to get the virus by touching a surface, like a contaminated doorknob, and then touching your own eyes, nose, or mouth.

When the flu virus enters the body, it uses hemagglutinin to bind to sialic acid sugars on the surface of epithelial cells in the upper respiratory tract.

Once bound, the cell swallows up the virus in a process called endocytosis.

That viral RNA is negative-sense, meaning that each piece first has to be transcribed by RNA polymerase into positive-sense mRNA strands, before it can be translated into proteins and assembled into viruses.

These viruses leave the cell by simply budding out from it by using the neuraminidase, which cleaves the sialic acid sugars in the membrane, releasing the newly created viruses from the cell.

Influenza symptoms start 1-4 days after infection and include fever, headache, runny nose, sore throat, and a cough.

Most of these symptoms get better in a week, but the cough often persists for up to two weeks.

There can sometimes be complications, though, like acute otitis media, bronchiolitis, croup, sinusitis, and pneumonia, including antibiotic-resistant strains caused by Staphylococcus aureus and Streptococcus pneumoniae.

The highest risk of complications is among high-risk groups like young children under 6 months of age, pregnant women, adults over 65 years old, and those with chronic medical conditions, like chronic heart or lung disease.