How does the coronavirus bypass the immune system? – 05/03/2023 – Balance and Health

Two new research has revealed the mechanisms by which coronaviruses evade the immune response.

Viruses use enzymes known as proteases to evade our immune system’s innate defenses, as these enzymes “turn off” the molecular signal that helps recognize areas on the surface of the virus where defense cells are active.

The research results were published last Tuesday (2nd) in the specialized magazine Science Signaling, from the Science group.

Coronaviruses are a group of viruses in the Coronaviridae family, of which the best known currently is Sars-CoV-2, the causative agent of the Covid pandemic. But there are six other coronaviruses known to infect humans, including the Sars and Mers viruses and four coronaviruses that cause the common cold.

In general, the effects of a coronavirus infection vary from asymptomatic cases with mild cold symptoms to a severe inflammatory condition that can lead to the need for hospitalization and mechanical ventilation assistance.

What will determine the effects of coronavirus infection is the amount of virus replicating in the body, the type of variant (some variants of Sars-CoV-2 cause more or less symptoms, as we saw during the pandemic) and the immune response of the our organism.

In the latter case, as the immune response is mainly against entry into cells, viruses are always mutating and looking for ways to evade this defense. One of these ways is to “hide” the region of the virus recognized by defense cells that would help trigger an immune response.

In the first experiment, conducted by scientists at Peking University, researchers identified enzymes known as PLPs (papain-like proteases) on the surface of several types of coronavirus. These PLPs had varying effects on the immune response against, for example, a cold coronavirus, where it was milder, and Sars-CoV-2, where the proteases were more potent and produced greater evasion of the immune response.

The mechanism involved in the action of proteases is known as Sting (or interferon gene stimulator). In general, interferons are molecular markers released in the face of an inflammatory process, as well as cytokines, which help the body to recognize a place where the invader is located – virus, bacteria or tumor cell – and attack it.

Because coronavirus proteases inhibit this molecular signal, interferons are not activated, and the immune response fails, thus allowing viral replication.

The experiment that followed sought to assess whether the use of a Sting-like molecule (called an agonist) in conjunction with a viral protease inhibitor prevented the replication of Sars-CoV-2.

When testing human lung cells with the two compounds, researchers at the Third People’s Hospital in Shenzhen, China, saw that this molecular combination blocked viral replication.

According to the researchers, this could be a target molecule in the search for new antivirals that have a more effective action in preventing the virus from multiplying in cells and reducing its infection.

Exhaust mechanism changes between variants?

As in the first experiment, the scientists saw that the different types of coronavirus have a different response regarding the action of proteases, the researchers also tested whether the different variants of Covid present the same “deactivation” process of the Sting mechanism.

The researchers also observed that in Sars-CoV-2, the proteases show small variations in their amino acid sequence. Covid alpha, beta, gamma and delta variants had different mutations in this region, but all were involved in the process of turning off the Sting, thus slowing down the immune response against the virus.

As many of the body’s defense mechanisms are aimed, at first, at recognizing the pathogen in the body through proteins found on the viral surface (called antigens), an antiviral that contains the different types of mutations found in the variants may be more effective. in preventing viral replication and ending the infection.

The authors conclude that the study is the first to unravel this complex cellular mechanism involved in recognizing and blocking the coronavirus that, when deactivated, can end up favoring the so-called immune escape.

“This Sting deactivation mechanism [sistema de interferons e citocinas molecular] appears to be the pathway through which human-infecting coronaviruses act to evade antibodies,” they state.