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Ancient Viruses In Our DNA Boost Immune System, Help Us Fight Infections

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The average human body is composed of 65 percent water with 11 percent hydrogen, 20 percent fat, and 8 percent ancient DNA from viral invaders, among many other heaps of factors.

Wait, what?

You read that right. Our DNA contains remnants of prehistoric battles between infectious viruses and our ancestors.

Millions of years ago, these viruses inserted their genes into our ancestors' genome, targeting sperm cells or egg cells and embryos.

The viral invaders, which are called endogenous retroviruses (ERVs), were passed down from generation to generation and had picked up mutations that canceled their ability to infect new cells. They eventually became permanent components of the human DNA.

ERVs were originally perceived to be genetic oddities without any real biological purpose. Now, a team of scientists from the University of Utah School of Medicine suggests that ERVs have become genetic weapons that fight against its own kind.

Evolutionary Irony

According to the team's study featured in the journal Science, ERVs are embedded in the genes that regulate mechanisms of our immune system, which is the first line of defense against pathogens and viruses. When these ERVs are removed experimentally, the immune system is crippled.

It's the greatest evolutionary irony: humans defend themselves from viruses with the evolved remains of ancient viruses.

Our immune system's ability to fight against foreign pathogens relies on a well-synchronized response, like a skilled tactician and commander in the battlefield.

When the person is infected, cells ring a silent alarm by discharging interferons, which are proteins that, in turn, trigger nearby cells to activate hundreds of genes that drive away viral invaders.

By studying genomic datasets of human cells, University of Utah researchers found that thousands of ERVs appear to be set off by interferons. As mentioned, when ERVs evolved over time, they had lost the ability to produce new infectious particles.

And so, researchers found one clue that may explain the ancient viruses' modern function: their location.

Instead of spreading aimlessly, ERVs were found to switch on immunity genes, creating new ports for interferons.

A Cell's Self-Destruction

Led by Edward Chuong, the research team tested whether ERVs were indeed crucial for immunity by using CRISPR/Cas9. They focused on one of the viruses known as MER41, which had infected an ancient primate about 50 million years ago. MER41 expanded so abundantly that each of us has 7,000 copies of it in our genes. Nearly 1,000 of it can attract interferons.

A copy of MER41 is close to a gene called AIM2, an important player in the immune system that detects when human cells are infected by bacteria or viruses. AIM2 forces cells to self-destruct to prevent the infections from spreading.

Chuong pointed out that this self-destruction sequence does not happen without MER41. He and his team used CRISPR/Cas9 to remove MER41 in the genes. They found that when the ERV was gone, the AIM2 lacked the ability to execute an effective immune system response against the infection.

Therefore, ERVs are indeed important in boosting the immune system's defense mechanisms, researchers said.

"It's likely no accident that innate immune systems reclaimed some of these viral remnants," said Nels Elde, Chuong's study co-author. "The evolutionary process turned the tables to our benefit."

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