Influenza Viruses and a Possible Flu Treatment Inspired by Llamas
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.
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.
- 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.
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 September, 2017, 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.
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.
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.
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.
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.
© 2018 Linda Crampton