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Influenza Virus Facts and a Possible Treatment Inspired by Llamas

Linda Crampton is a writer and teacher with a first-class honors degree in biology. She often writes about the scientific basis of disease.

Antibodies in llama blood may help us to create a better flu treatment.

Antibodies in llama blood may help us to create a better flu treatment.

Influenza Viruses and the Flu

Influenza viruses are responsible for the respiratory illness known as influenza, or the flu. The viruses cause a lot of misery in humans. Even worse, they are sometimes deadly. Vaccines to prevent the flu exist as well as treatments for the illness if it develops. These can be helpful, but they aren’t always successful. One reason for this lack of success is the existence of many types of flu viruses. Another is the fact that they mutate (change genetically) very rapidly compared to many other viruses that cause disease.

A more effective way to attack influenza viruses while they are inside a person’s body would be a great development. New research suggests that antibodies derived from ones in llama blood may provide us with this improved treatment. The antibodies might be able to destroy multiple types of flu viruses. In a recent experiment, the new treatment was found to be very effective in mice. More research is needed before clinical trials are performed in humans, however.

The H1N1 or swine flu virus (a colourized transmission electron micrograph)

The H1N1 or swine flu virus (a colourized transmission electron micrograph)

Types of Influenza Viruses and Their Effects

There are four known types of influenza viruses.

  • Type A is the most serious one for humans because it has caused pandemics as well as epidemics. It infects some animals as well as humans. (The H1N1 virus is a subtype of Type A.)
  • Type B affects only humans and causes epidemics.
  • Type C affects humans and some animals. It causes a mild respiratory illness.
  • Type D affects cows and doesn't appear to infect humans.

An epidemic is an outbreak of a disease that affects many people in a large area of a country. A pandemic affects people in multiple countries around the world.

The Most Recent Pandemics

According to the CDC (Centers for Disease Control and Prevention), there have been four flu pandemics since 1900.

  • The most deadly pandemic since 1900 was the co-called "Spanish flu" of 1918. The outbreak is estimated to have killed 65,000 people in the United States and fifty million people around the world.
  • In 1957, the "Asian flu" killed around 116,000 people in the United States and 1.1 million in the world.
  • In 1968, the "Hong Kong flu" killed about 100,000 people in the U.S. and around a million people around the world.
  • The last pandemic was in 2009. In the first year during which the virus circulated, an estimated 12,469 people in the United States died from the disease and between 151,700 and 575,400 people worldwide. A novel strain of the H1N1 virus was the cause of the pandemic.

Researchers suspect that it's only a matter of time before another flu pandemic develops. This is one reason why understanding the disease and creating new and more effective ways of dealing with it are so important.

Subtypes and Strains of Flu Viruses

Influenza viruses have two important protein molecules on their surface. These proteins are hemagglutinin (HA) and neuraminidase (NA). On a page that was last updated in November, 2019, the CDC says that 18 versions of HA and 11 versions of NA exist. Some other sources give smaller numbers. Flu viruses are classified into subtypes based on the proteins that coat them. For example, influenza A subtype H3N2 has version three of the hemagglutinin protein and version two of the neuraminidase protein on its surface.

To complicate matters even further, each subtype of flu virus exists in the form of multiple strains. Strains are slightly different from one another genetically. The difference can be very significant with respect to disease symptoms and seriousness, however.

The relevance of the different subtypes and strains to human infections changes over time. New forms of the virus appear and old forms disappear as mutations occur. A flu vaccine may no longer work against a mutated virus or a new strain.

Although many different combinations of the HA and NA proteins are possible, viruses with only a few of the possible combinations circulate through the human population at any given time.

— Baylor College of Medicine

Structure of a Virus

Viruses don't consist of cells. They are sometimes considered to be non-living because they can't reproduce without entering a cell and using its equipment to make new virus particles. Some scientists do consider viruses to be living organisms because they contain genes, however.

Genes contain instructions for making proteins. The proteins control the structure and behaviour of an organism to a greater or lesser extent, depending on the type of organism. The genetic code for making proteins is "written" in a sequence of chemicals, which is reminiscent of a written language consisting of a sequence of letters. The code is usually stored in DNA (deoxyribonucleic acid) molecules, but in some organisms it's stored in RNA (ribonucleic acid) molecules instead.

The individual entities or particles of a virus as they exist outside our cells are often called virions. The key parts of a virion are a core of nucleic acid covered by a coat of protein, which is known as a capsid. The nucleic acid is either DNA or RNA. Influenza viruses contain RNA. Type A and type B flu viruses contain eight RNA strands while the type C virus contains seven. In some kinds of viruses, a lipid envelope surrounds the capsid.

Influenza virions are usually round in shape, though occasionally they are elongated or irregularly shaped. They have a capsid made of protein spikes on their surface. Some of the spikes are made of hemagglutinin and the others of neuraminidase.

Influenza viral cell invasion and replication

Influenza viral cell invasion and replication

Infection of a Cell by an Influenza Virion

Once influenza virions have entered our body, they attach to sugar molecules that are part of the glycoproteins located in the membrane of a cell. In humans, the cells that are attacked are generally ones lining the nose, throat, or lungs. Once it has attached to the membrane, a virion enters the cell and triggers it to make new virions by co-opting normal processes in the cell.

The viral replication process is simplified and summarized below. The process is impressive. The virion not only "persuades" the cell to let it enter but also forces it to make components of new virions instead of its own molecules. Some details of the process aren't fully understood yet.

  • The hemagglutinin molecules of the virion join to molecules on the surface of the cell membrane.
  • The virion is transported into the cell by a process called endocytosis. In endocytosis, a substance is moved into a cell inside a sac called a vesicle, which is created from the cell membrane. The membrane is repaired afterwards.
  • The vesicle opens inside the cell. The viral RNA is sent into the nucleus of the cell.
  • Inside the nucleus, new copies of the viral RNA are produced. (Normally, human RNA containing the code for making proteins is made in the nucleus based on the code in the DNA. The process of making RNA is known as transcription.)
  • Some of the viral RNA leaves the nucleus and goes to the ribosomes. Here proteins are made based on the code in the RNA molecules. The process is known as translation.
  • Viral RNA and protein coats are assembled into virions by the Golgi apparatus, which acts like a packaging plant.
  • The new virions leave the cell by a process known as exocytosis, which can be thought of as the opposite process to endocytosis. The process requires the neuraminidase located on the surface of the virions in order to be successful.
  • The released virions infect new cells unless they are stopped by the immune system.

The symptoms that develop from an influenza virus infection are created by the reaction of the body's immune system to the virus instead of by the actions of the virus itself.

Genetic Changes in the Virus: Drift and Shift

Mutations happen due to a variety of reasons. Both external factors and mistakes in internal processes in cells can cause genetic changes. In influenza viruses, processes known as drift and shift are important in changing the virus genetically and causing it to make altered proteins.

Antigenic Drift

Drift is more specifically known as antigenic drift. (An antigen is a chemical that triggers the production of an antibody). As the virus takes over the cell's equipment and reproduces, small genetic mistakes that cause slightly different forms of HA or NA to be made may occur. As these changes accumulate, they may eventually mean that our immune system can no longer recognize the virus and doesn't attack it. Drift is one reason why new flu vaccines are required each year.

Antigenic Shift

Shift (or antigenic shift) is a rapid and much more extensive change in the viral proteins than antigenic drift. The proteins are so different from their former form that the human immune system mounts almost no immune response to the virus. The situation can develop when a cell is infected by two different viral subtypes or strains at once. RNA from the different varieties of the virus may become mixed up in the host cell. As a result, the new virions may have strands of RNA from different subtypes or strains of viruses. Shifts can cause serious effects and can trigger pandemics. Fortunately, they are rarer than drifts.

Potentially Useful Antibodies in Llama Blood

Antibodies are proteins in the immune system that help to fight invading bacteria, viruses, or other pathogens (microbes that cause disease) in an animal's body. The human antibodies that attack influenza viruses bind the to the head (tip) of the hemagglutinin molecules on the surface of the virions. Unfortunately, this is a highly variable area in the various versions of flu viruses and is also the part of the molecule that most often changes when the viruses mutate. If the head changes significantly or is of a type not recognized by the immune system, antibodies won't be able to join it.

Researchers have discovered that llama antibodies to flu viruses are much smaller than human ones. They can travel between the protein spikes on the outside of an influenza virion and join to the tails, or lower section of the proteins. The tails have a relatively constant composition and are said to be highly conserved in the different flu viruses. This means that even if the heads of the proteins change, llama antibodies may still be protective.

Creation of a Synthetic Antibody

Researchers led by a scientist at the Scripps Research Institute in California infected llamas with multiple types of flu viruses. They then took blood samples from the animals and analyzed them for antibodies. They looked for the most powerful ones that could attack multiple strains of flu virus. Four types of antibodies met their criteria.

The scientists created an artificial antibody containing the significant parts of all four llama antibodies. The synthetic antibody had multiple binding sites and was able to join to hemagglutinin from both type A and type B flu viruses.

The researchers administered their synthetic antibody to mice given deadly doses of sixty influenza virus subtypes and/or strains. The molecule was administered intranasally. Amazingly, the antibody destroyed all of the viruses except one, and that was a kind that doesn't currently infect humans.

One feature that distinguishes llamas from alpacas is their banana-shaped ears.

One feature that distinguishes llamas from alpacas is their banana-shaped ears.

A Universal Flu Treatment

A truly universal treatment would be able to destroy all types of influenza virus. That would be a wonderful but difficult achievement. The Scripps Research Institute scientists may have created an antibody that attacks a far wider variety of hemagglutinin molecules than current antibodies in humans, however.

As impressive as the initial results are, more work needs to be done. We need to know whether the antibody works in humans. It needs to bind to hemagglutinin and neutralize the virion as a result. The fact that this happens in mice is a hopeful sign, but it doesn't necessarily mean that it will work in humans. We also need to discover whether the antibody is safe for humans as well as how easy it would be to mass produce the antibody and how expensive this production would be. The additional research might be very worthwhile.

Though most of us recover from flu, a significant number of people don't. People with weakened immune systems are most likely to experience harmful effects from flu viruses. People over the age of sixty-five are especially susceptible to harm. In a pandemic, even younger people whose immune system is functioning well are at risk. We need new treatments or preventative methods for influenza.

References

  • Information about the flu and influenza viruses from the CDC
  • Flu virus facts from the Baylor College of Medicine
  • Information about the virus from Florida State University
  • Past pandemics from the CDC
  • Llama blood clue to beating flu from the BBC (British Broadcasting Corporation)
  • Universal protection against influenza from the Science journal (published by the American Association for the Advancement of Science)

This content is accurate and true to the best of the author’s knowledge and does not substitute for diagnosis, prognosis, treatment, prescription, and/or dietary advice from a licensed health professional. Drugs, supplements, and natural remedies may have dangerous side effects. If pregnant or nursing, consult with a qualified provider on an individual basis. Seek immediate help if you are experiencing a medical emergency.

© 2018 Linda Crampton

Comments

Linda Crampton (author) from British Columbia, Canada on March 02, 2020:

Hi, Denise. Where I live, health organizations note the strains of flu virus that have been circulating in the local community lately and predict which ones are likely to be common in the upcoming flu season. Then they create a vaccine for those strains.

The prediction system seems to be quite good, but it's not perfect and is better in some years than others. Doctors here say it's helpful to get a flu shot because it does protect us from at least some of the strains that we are likely to encounter.

Viruses may seem to be simple compared to humans, but their behaviour is actually quite complex. As you say, more research needs to be done. I'm sorry that your grandfather lost his sister in the 1918 flu pandemic.

Blessings to you as well, Denise.

Denise McGill from Fresno CA on March 02, 2020:

What good then is getting the flu shot when there are so many strains and substrains that exist? I realize the shot is supposed to built up antibodies in the immune system but doesn't really attack specific strains, right? More research needs to be done. My grandfather's sister (age 18) died in the 1918 influenza pandemic/Spanish flu. He always spoke of her. Her loss affected him profoundly.

Blessings,

Denise

Linda Crampton (author) from British Columbia, Canada on June 08, 2019:

Yes, the discovery sounds like an excellent reason to hug a llama! Thank you for the comment.

RTalloni on June 08, 2019:

Well, if we never had a reason to hug a llama before, we do now! If I had a llama I would name him Bravo in honor of this information. Thanks for another interesting read with hopeful information. Viva llama research!

Linda Crampton (author) from British Columbia, Canada on November 26, 2018:

Thanks for the comment, Peggy. I'm hoping that the llama research will be very useful.

Peggy Woods from Houston, Texas on November 26, 2018:

We always take the flu shot each year even though it is not 100% effective. It would be wonderful if a vaccine from llama blood would be universally effective. The best part of all would be that llamas would not be harmed. Your articles are always so informative.

Linda Crampton (author) from British Columbia, Canada on November 18, 2018:

Thank you for sharing the information, Bede. I very much hope that humans receive the same benefit as the mice.

Bede from Minnesota on November 18, 2018:

Linda, I became aware of the Spanish flu several months ago when I was doing research for an article. Two saints (who were siblings) died from it. Apparently, soldiers returning home spread the virus, which made the death toll so high.

The Scripps’ discovery is amazingly hopeful. Let’s hope that humans can receive the same benefits as mice.

Linda Crampton (author) from British Columbia, Canada on November 17, 2018:

I think it's amazing as well. Nature seems to have so much to offer us. I appreciate your visit, Natalie.

Linda Crampton (author) from British Columbia, Canada on November 17, 2018:

Hi, Rajan. I think it would be great if a vaccine that protected us from more flu strains existed, too. We need better vaccines. Thanks for the visit.

Natalie Frank from Chicago, IL on November 17, 2018:

It always amazes me where we find treatments and cures for different problems. Thanks for a fascinating article.

Rajan Singh Jolly from From Mumbai, presently in Jalandhar, INDIA. on November 17, 2018:

Very informative article. It would be great if a safe vaccine that can provide protection against far more virus strains than now is developed. Thanks for sharing the new research that is being done.

Linda Crampton (author) from British Columbia, Canada on November 16, 2018:

Hi, Chitrangada. Thank you for the kind comment. I hope the llama research is helpful, too.

Chitrangada Sharan from New Delhi, India on November 16, 2018:

Thanks for sharing this excellent and informative article about Influenza.

You always come up with the latest updates in the medical field and I appreciate your well researched articles. I hope the llamas are helpful.

Thanks for sharing.

Linda Crampton (author) from British Columbia, Canada on November 15, 2018:

I appreciate your comment, Nithya. Thank you for the visit.

Nithya Venkat from Dubai on November 15, 2018:

Interesting, Llama blood can be the answer to viral infections that wreak havoc. I hope the researchers come up with an effective solution. When the immune system becomes weak then the virus takes over the body system and worsens the condition. Interesting and informative as always. I always something new in the research field when I read your articles, thank you for sharing.

Linda Crampton (author) from British Columbia, Canada on November 15, 2018:

Thank you very much for the comment, Eman.

Eman Abdallah Kamel from Egypt on November 15, 2018:

A very interesting and informative article about the flu. Influenza in some cases is serious, thank you for sharing the information.

Patty Inglish MS from USA and Asgardia, the First Space Nation on November 14, 2018:

@Nell Rose - Fortunately, my grandfather and father both survived the Spanish Flu. I often wonder if they somehow passed antibodies down to me, since I've never had the flu at all, but I don't know if that is possible.

Linda Crampton (author) from British Columbia, Canada on November 14, 2018:

Hi, Nell. It is a scary thought that such a tiny particle can cause so much harm. I hope the flu shot works for you this year.

Nell Rose on November 14, 2018:

Really interesting Linda. I actually had a flu shot this year for the first time in years purely because I caught the flu from/just after the jab I had about 3 years ago. Its scary stuff, and to think such a tiny thing can cause so much illness. Yes that Spanish Flu was awful! It killed more people than the whole of the first world war.

Linda Crampton (author) from British Columbia, Canada on November 14, 2018:

Thank you very much for the comment and for sharing the interesting information, Patty.

Patty Inglish MS from USA and Asgardia, the First Space Nation on November 14, 2018:

Thanks for the article Linda! I really appreciate reading such updates and discoveries in medical and health research.

@FlourishAnyway -- At my medical school in Ohio, researchers looked at so many cross-species diseases that someone thought it wise to look also at possible cross-species preventatives like possible vaccines. I think that this probably occurred across the nation as well. Pretty neat, isn't it?

Linda Crampton (author) from British Columbia, Canada on November 14, 2018:

Your 2009 experience sounds horrible, Flourish. I don't know why the researchers chose the llama for their research, but I'm guessing that they had already discovered that the animal's immune system has some interesting features.

FlourishAnyway from USA on November 14, 2018:

The current flu vaccine seems to be very hit and miss. Having been one of those who got really sick from the 2009 flu pandemic, I hope they figure out more effective vaccines. I was out of work for a week and still not 100% for a month. I wonder how in the world they even thought about llamas or other animals for this?

Linda Crampton (author) from British Columbia, Canada on November 14, 2018:

Hi, Heidi. A universal flu solution would be a great development. I hope it happens. Thank you for the comment.

Linda Crampton (author) from British Columbia, Canada on November 14, 2018:

Thank you, Manatita. I hope llamas can help us, too. We need more ways to protect people from the flu.

Linda Crampton (author) from British Columbia, Canada on November 14, 2018:

Thank you, Pamela. The lupus flare-up sounds bad. I'm glad you get the flu vaccine!

Heidi Thorne from Chicago Area on November 14, 2018:

I do hope that a universal flu solution is developed. (I remember the Hong Kong flu days.) Interesting that the llamas are a key in this equation. Thanks for sharing this important development!

manatita44 from london on November 14, 2018:

Very useful information and with tremendous promise. I work in a hospital and the authorities are very active at this time, trying to canvas for more staff to take the vaccine. Some do, but some of us humans have all kinds of reasons for not wanting to. They vary from conspiracy theories, to fear of getting worse. Hope that the llama can in fact help us. Great work!

Pamela Oglesby from Sunny Florida on November 14, 2018:

I always get the flu vaccine as one time a couple of decades ago I didn't get one and got a serious case of the flu. That resulted in a big lupus flare-up.

Linda, the details in this article are so interesting, and I know you must have been a lot of time in gathering this information, then putting into a framework that makes sense to all of us too. Llamas were the surprise.

Linda Crampton (author) from British Columbia, Canada on November 13, 2018:

That sounds like a bad situation for people who want and need a vaccination. Thanks for commenting, Liz.

Liz Westwood from UK on November 13, 2018:

This is a very topical article, as in the UK people are rushing to get their flu jabs amid rumours that there is a shortage of vaccine for over 65s.

Linda Crampton (author) from British Columbia, Canada on November 13, 2018:

Thank you so much for such a kind comment, Bill. I would love to have my own llama. I meet them every year at the fair at the PNE, but that's my only contact with them.

Bill Holland from Olympia, WA on November 13, 2018:

I don't tell you enough, Linda, but I absolutely love your articles. They are always interesting.

How about an article on llamas? We have one out at the farm, and they are fascinating animals. :) Just a suggestion.

Linda Crampton (author) from British Columbia, Canada on November 13, 2018:

Hi, Mel. I appreciate your comment. We may have a lot to thank llamas for!

Linda Crampton (author) from British Columbia, Canada on November 13, 2018:

Hi, Mary. Thank you very much for reading the article. I hope the study does save many lives.

Mel Carriere from San Diego California on November 13, 2018:

Thanks for this wonderful primer on the flu. I will heretofore look upon llamas in a new light.

Mary Norton from Ontario, Canada on November 13, 2018:

This is a very interesting study Linda. who would ever think we'll get those antibodies from llamas? You are right that many don't recover from flu and so this study will save many lives.

Linda Crampton (author) from British Columbia, Canada on November 12, 2018:

Thanks for sharing your suggestions for staying healthy, Jackie. They sound like great ideas. I hope the researchers complete their study soon as well. I'll be watching, too!

Jackie Lynnley from the beautiful south on November 12, 2018:

Though I have never had a flu vacination this does sound interesting and I will look more into it. Maybe just luck or something more, I don't know but keeping my hands sterile outside of home, not going into crowded places and eating no handled food out anywhere in flu season has kept me flu free for well over 10 years.

Hope I won't be sorry but as I say what you have written here is something new and worth considering. Hope they complete the study soon and I will be watching, Thanks for bringing it to attention, Linda!

Linda Crampton (author) from British Columbia, Canada on November 12, 2018:

Hi, Dora. I think it's an exciting possibility, too, though like you I don't want the animals to be harmed. I hope the synthesized antibody does what is needed.

Dora Weithers from The Caribbean on November 12, 2018:

The flu is a regular health nuisance every year,and it would be great if it can be remedied by blood drawn from the animals without killing them or putting them at risk. Excited about the possibility! Thanks for sharing hope.