Animal viruses have a secret ally to infect human cells

Viruses, those tiny invaders that work their way into host cells, are a miracle of biological survival. Among them, arteriviruses, which are found in a variety of animals around the world, have attracted great interest.

These viruses are currently largely inaccessible to the human immune system. A recent study has revealed an intriguing mechanism by which arteriviruses sneak into host cells and initiate infection.

Friendly protein became the enemy

At the center of this microscopic drama is a protein found in mammals – an unsuspecting gatekeeper that inadvertently opens the door for arteriviruses.

The research team also discovered a monoclonal antibody – an ally of the immune system – that binds to this protein and effectively protects cells from viral infections.

Arterivirus infections

Why should we care about arteriviruses? These are viruses that we have no immunity to.

“It's important to remember that we are essentially immunologically naïve in that we have no known arteriviruses that infect people, so we cannot rely on pre-existing immunity to help us,” said co-lead author Cody Warren , assistant professor of veterinary biosciences at The Ohio State University (OSU).

To understand the seriousness of the situation, we must consider the possible impacts. Arteriviruses are found in various mammals such as non-human primates, opossums, pigs and horses. They are often present without causing any apparent illness.

However, when they switch hosts, the viruses can cause serious health problems such as pneumonia, hemorrhagic fever or encephalitis.

Travel of a virus in a cell

In the field of viruses, intrusion and penetration is a gradual process. In arteriviruses, the first stop is the FcRn receptor, a protein complex formed by the meeting of two genes – FCGRT and B2M. Otherwise, this receptor plays a harmless role by transporting antibodies across the placenta to the fetus.

However, when a virus occurs, the FcRn receptor becomes the channel of infection. It is responsible for the introduction of at least five different arteriviruses that infect monkeys, pigs and horses.

When the researchers disrupted the FCGRT gene, the main component of the FcRn complex, the cells became resistant to the infection. Better yet, pretreating the cells with monoclonal antibodies against FcRn protected them completely.

Arteriviral infection of host cells

This story has a fascinating genetic subplot. It turns out that the susceptibility of mammalian hosts to arterivirus infection varies due to differences in the genetic sequence of their FcRn.

Essentially, the sequence variations of this receptor protein can either facilitate or complicate cross-species infections.

The surface protein CD163, which has historically played a gatekeeper role for simian hemorrhagic fever virus (an arterivirus), also came into the spotlight in this study.

Experiments showed that CD163 interacts with FcRn and helps in arteriviral infection of host cells. By identifying these arterivirus infection steps, we have reached an important milestone.

“When we look at the biology of viruses, entry mechanisms are one of the most important things we can understand. Because if you can stop a virus’s ability to infect a cell by disrupting the initial virus-receptor contact, you now have a potential therapeutic strategy,” Warren said.

We are preparing for the next pandemic

By uncovering the secrets of how arteriviruses invade host cells, we will be better prepared for future viral threats.

With an existing monoclonal antibody that can prevent viral infections in cells, we have a glimmer of hope in our pandemic preparedness toolkit.

“If any of these viruses appeared in humans, I think we would be in big trouble. That’s the motivator for me,” said Adam Bailey, assistant professor of pathology and laboratory medicine at the University of Wisconsin-Madison and co-lead author of the study.

Significance of the study

Knowledge is indeed power. As we deepen our understanding of how viruses infect cells, we will move closer to better prevention methods and, ideally, fewer global health crises.

“Understanding the nuances of species-specific FcRn usage will be important for predicting arterivirus spillover to new hosts, as our data suggest that FcRn may act as a molecular barrier against cross-arterivirus infections,” the researchers write.

The study is published in the journal Nature communication.

—–

Did you like what you read? Subscribe to our newsletter for exciting articles, exclusive content and the latest updates.

Check out EarthSnap, a free app from Eric Ralls and Earth.com.

—–