How the Influenza Virus Causes Disease


By Barry C. Fox, M.D.University of Wisconsin

The influenza virus is an RNA virus. Like all viruses, it can’t replicate by itself. It needs to take over the protein machinery of a living cell and reprogram the cell to create more virus particles, usually inducing cell death. This type of virus (Type A) is covered with foreign protein spikes on its outer surface.

#-D rendition of a virus floating in a cellular environment
Like other viruses, the influenza virus doesn’t replicate by itself. (Image: ffikretow/Shutterstock)

The Influenza Virus Inside the Cell

One type of spike is used as a hook by the virus to attach itself to the outside of a host cell. The cytoplasmic membrane of the cell next engulfs the virus and pulls it inside. Through a complicated series of maneuvers, including uncoating of the virus—where the RNA slips out of its viral coating, the virus tricks the host cell to let the viral RNA into the cell, and once this occurs, the virus is in control. 

Remarkably, within about 12 hours of hijacking the cell, the influenza virus can release up to one million new viruses. Now that’s what you can call efficient reproduction. With such a rapid rate, there is a high possibility for genetic mutations.

The antiviral medications Amantadine and Rimantadine were effective for the influenza A virus for years. Both medications inhibited virus replication by interfering with the viral uncoating process heading inside the cell.  Importantly, the high rate of mutations of influenza A has led to the emergence of widespread resistance to both of these antiviral medications, so much so that neither is used for treatment anymore.

This is a transcript from the video series An Introduction to Infectious DiseasesWatch it now, on Wondrium.

Effectiveness of Antiviral Medications

Sick middle-aged woman sneezing in bed
Fortunately, effective antiviral medications against Influenza exist. (Image: fizkes/Shutterstock)

Antiviral medications known as neuraminidase inhibitors are fortunately still effective in shutting down virus replication. Oseltamivir and zanamivir are two of these antivirals, and others are being developed. They work against influenza A, and so far, the viruses have shown a very low mutation rate against them. 

The antivirals inhibit the release of the virus from the host cell by blocking neuraminidase, so the viruses are trapped inside. When these antivirals are given within the first 72 hours of influenza illness, they can shorten the duration of clinical illness by one or two days. They have been shown to reduce the rate of secondary bacterial infections of the lung as well.

Antiviral medications are also deemed to be helpful in those unfortunate enough to be hospitalized for influenza, even when the 72-hour window has expired. In general, the earlier they’re given, the more clinical benefit antivirals are likely to have. 

During the 1918 Spanish Flu, while most patients subsequently recovered, some had a relapsing respiratory problem. Ironically, many victims died from a secondary bacterial infection rather than from actual influenza.

Learn more about the history of antibiotic development

How Did the Spanish Flu Get Out of Hand?

A black-and-white photo of Spanish flu patients in beds next to each other in a large building
The Spanish flu had mutated through intermediate hosts like birds. (Image: Armed Forces Institute of Pathology/National Museum of Health and Medicine/Public domain)

So, why was the Spanish Flu virus so virulent? The National Institute of Allergies and Infectious Diseases has been researching the answer to this question. They even retrieved gene sequences of the 1918 flu virus from victims buried in Alaska’s permafrost. Note that this work was done in a high-level biosafety lab to ensure the virus was well contained so as to not start another pandemic.

Using eight of the original genes, researchers genetically reverse-engineered the virus, then injected it into mice. They found that the virus was much more lethal than usual to mice, but this did not explain the mechanism of extreme virulence. Using current studies of bird, or avian influenza, one of the mechanisms of lethality may have been discovered. A receptor protein of the 1918 flu virus was very similar to a modern version of the avian flu, which may help explain its virulence.

An unusual quality of avian influenza is that the bird virus proteins are not usually able to bind well to the human throat receptors. Scientists believe that in order for the virus to leap from birds to humans, they have to pass through an intermediate animal that contains both bird and human receptors, like a pig, for example. However, the 1997 avian bird flu outbreak showed that an intermediate host might not be needed since that virus could jump directly to humans.

Learn more about emerging and reemerging diseases.

Flu Pandemics Love Air Travel

A pandemic is usually caused by a new strain of the virus or a reappearing one. These viruses either have never circulated among humans before, or they circulated many years ago. So either humans have no immunity against it, or very little. This makes the virus easy to spread.

All influenza pandemics since 1918 have been caused by viruses with RNA genetic remnants of the 1918 virus. In addition, all of them also contained RNA from swine. So in a way, the 1918 pandemic earned the right to be called the mother of all pandemics. 

The last century saw four influenza pandemics, which spread to all countries within 6 to 9 months. The other 3 were the 1957 Asian flu, 1968 Hong Kong flu, and the 2009 Mexican flu. Since the speed and frequency of air travel have significantly increased since the 1960s, a much faster spread of influenza was seen in the 2009 pandemic.

Pandemic viruses can also originate when some of the genes from animal flu viruses mix with genes from human flu viruses to create a whole new hybrid. This happens when an animal or person is co-infected by both a human virus and an avian flu virus at the same time. The process of combining viruses is called reassortment. The 2009 Mexican flu virus was actually a combination of swine, bird, and human flu viruses.

Common Questions about How the Influenza Virus Causes Disease

Q: Why does Influenza have a high potential for mutation?

Due to the mechanisms the Influenza virus uses, it can produce up to one million new viruses 12 hours after penetrating the cell. This highly increases the chances of mutation.

Q: Why don’t Amantadine and Rimantadine work on Influenza anymore?

Because of the high rates of mutation in the Influenza virus, widespread resistance to these medications has occurred. But fortunately, other medications are available.

Q: Why was the spread of the 2009 pandemic much faster than the previous ones?

Because travel has increased throughout the world, especially air travel. In addition, the speed of travel has increased, helping the spread of the Influenza virus.

Keep Reading
Anti-Retroviral Therapy: Treating HIV and AIDS
HIV Prevention: Precautions, Education, and Vaccines
AIDS: The Symptoms of an HIV Infection