Can the COVID19 Virus Alter Our DNA?

What the 1918 Spanish Flu pandemic tells us about the genetic consequences of viruses

Can viruses alter our very genetic code, effectively hijacking and hiding in our cells for generations and how does this affect the health of future generations? Could viruses be mutating us, cell by cell? Sounds like science fiction, doesn’t it?

To answer these questions conclusively, we need to first go back to 1918 and the greatest killer of all time. I’m not referring to the First World War, but rather the Spanish Influenza.

The 1918 Spanish Flu Pandemic

It killed between 50 and 100 million people in three pandemic waves between 1918 and 1919. The chart below shows death rates in a some of the affected areas.

Graphic courtesy of AGN

As with other 20th-century epidemics and pandemics, such as HIV/Aids, Africa and Asia suffered proportionately more than European and North America.

Whilst the average case mortality in the developed world was about 2%, in India, where 18.5 million perished, it was 6%, and in Egypt, where 138,000 died, it was 10%. If we adjust for population growth, in today’s world the Spanish Flu would have claimed between 200 million and 425 million people.

So called, not because it originated in Spain, but because Spain was the only country to openly speak about the pandemic, the Spanish Flu was unusual. Unlike traditional influenza outbreaks it targeted healthy individuals between the ages of 15 and 40, sparing the aged.

Thanks in no small part to people like Jeffrey Taubenberger, a molecular pathologist at the National Institute of Allergy and Infectious Diseases who has been studying the 1918 virus for nearly thirty years, we now have a much better idea of exactly what the world was dealing with.

In the late 1990s, he succeeded in retrieving fragments of viral RNA from stored pathology specimens taken from American soldiers who had died of flu at a US army camps in 1918 and an Inuit woman who’d been buried on a beach in Alaska, where the permafrost had preserved her lung tissue from decay.

The discovery of H1N1

In 2005, Taubenberger and his colleague, Anne Reid published the virus’s genetic sequence. Their findings were a shock. Previously, epidemiologists had observed that flu pandemics were preceded or followed by outbreaks of influenza-like illnesses in dogs, cats, and horses. It was also known that from time to time flu viruses could infect pigs and, of course, humans, and that wild flu viruses circulated in migratory waterfowl.

When Taubenberger analysed the genome of the Spanish flu, he found that most of its genes were derived from a bird flu virus. Taubenberger considered the H1N1 virus so ‘avian-like’ he could not discount the possibility that it had transmitted directly from birds to humans shortly before 1918 and perhaps as early as 1916.

The source of the outbreak is still a matter of debate. The genes map most closely to wild waterfowl from North America but, despite examining the Smithsonian Institute’s extensive bird collections, Taubenberger was not able to find viable autopsy remains from before 1918.

One theory suggests ‘spillover’ May have occurred in early 1918, not far from an army camp in Kansas that supplied soldiers to the American Expeditionary Force. Another option favoured by British virologist John Oxford, is that the pandemic began at Étaples, a huge British military camp an hour south-west of Boulogne.

Why does all of this matter?

Why should we be concerned with these facts? After all, the virus did not survive, did it?

It has survived. We simply did not know what to look for before it was correctly identified. Genes from the Spanish flu continue to circulate in both human and pig populations to this day. Some of these genes are direct descendants of the 1918 virus whilst others have reassorted with other pandemic viruses, such as the 1968 Hong Kong flu and the hybrid H1N1 virus responsible for the 2009 swine flu pandemic which originated in the USA.

It matters because, in mice, the H1N1 Spanish flu is extremely virulent, generating 39,000 times more virus particles than a modern flu strain. Research has shown that by targeting the immune response in infected mice they can be protected but humans still remain at risk.

How is it possible though that the virus continues to be carried by human hosts a hundred years later? How has this happened and what mechanisms have enabled this. Has it become a part of our genetic code and if so, how does this process occur? More importantly, what have the consequences been to the carriers and their descendants?

Are we carrying the seeds for future epidemics in our own genes and has the viral world discovered the perfect hiding place whilst it waits? Inside its hosts?

To understand the processes at work here we first need a little basic science on human genes, chromosomes and how our DNA functions. It might get a little hairy here, but I’ve tried to simplify this as much as possible.

Understanding Cells, Chromosomes, Genes and DNA.

This topic gets complicated really quickly so for ease of understanding, here’s the simple version and if you keep to the ordering above, it will help you understand how they tie together.

All life is made up of cells. All cells in the human body, except red blood cells, contain chromosomes.

The word ‘chromosome’ comes from the Greek words khroma meaning “color” and soma meaning “body”. Laboratory experiments in the 1880s revealed chromosomes could be easily stained with dyes, thus making studying them easier. Hence the name.

Let’s recap. Cells, and inside these, chromosomes. On each of these chromosomes, we find a gene. You know genes as the traits you pass on to your children. These are unique instructions for hair colour, height, and all the other features that make you, well, you.

Every factor in inheritance is due to a particular gene. Genes specify the structure of particular proteins that make up each cell. Gene comes from the Greek word genea meaning generation, origin, beginning, kin, or sometimes race. Gene was shortened from “pangene” which means “all-generation”.

Finally, Genes contain DNA (deoxyribonucleic acid). DNA is the chemical basis of heredity.

Again, for clarity. DNA is in genes, genes are on chromosomes and live in our cells. You’ve probably heard of the Human Genome Project. This was a project undertaken to map all genes and chromosomes in a human. The combination of gene and chromosome gives it its name – Genome.

For those of you who wish to explore the topic in more depth, here is an excellent and still reasonably easy to follow article from Nature on DNA structure.

We’re going to head off now on what may appear at first to be a tangent, but the reason for this will become clearer as you read.

Genetic conditions and Gene Therapy

Gene therapy is an experimental technique that uses genes to treat or prevent disease. In the future, this technique may allow doctors to treat a disorder by inserting a gene into a patient’s cells instead of using drugs or surgery. Researchers are testing several approaches to gene therapy, including:

Replacing a mutated gene that causes disease with a healthy copy of the gene.

Inactivating, or “knocking out,” a mutated gene that is functioning improperly.

Introducing a new gene into the body to help fight a disease.

Gene therapy is currently only considered as a treatment for diseases or conditions that do not respond to conventional medicine.

Several inherited immune deficiencies have been treated successfully with gene therapy. Most commonly, blood stem cells are removed from patients, and retroviruses are used to deliver working copies of the defective genes. After the genes have been delivered, the stem cells are returned to the patient.

Because the cells are treated outside the patient’s body, the virus will infect and transfer the gene to only the desired target cells.

The conditions where gene treatment is offering the most hope include Fat metabolism disorder, Parkinson’s, Auto-Immune disorders, Cancer, Blood Disease, Hemophilia, Hereditary Blindness and others. For a more detailed overview consult this article from the Genetics department at the University of Utah

So now you’re probably wondering why viruses feature in gene therapy and what exactly are retroviruses? Let’s examine that in a little more depth.

Viruses and Retroviruses

Viruses, or more accurately retroviruses, play an essential role in gene therapy. This is because of a virus’s ability to penetrate cells and affect changes on a cellular level within the human body.

Viruses are tiny microbes that can infect cells. Once in a cell, they use cellular components to replicate. They can be classified according to several factors, including:

the type of genetic material they use (DNA or RNA)

the method they use to replicate within the cell

their shape or structural features

Retroviruses are a type of virus that use RNA as their genetic material and a special enzyme called reverse transcriptase to translate the virus’s genetic information into DNA.

That DNA can then integrate into the host or your cell’s DNA. At this point, the retrovirus can replicate itself using your cell’s resources.