Little more than a century has passed since the discovery of the first virus - thanks to the work of Dimitri Ivanovski - until the appearance of the SARS-CoV-2, technical name of the virus. Although our knowledge of viruses is little more than a century old, these microorganisms have accompanied humans for millions of years of evolution.
In all that time we have always had a faithful ally to face them: the immune system. But could our best ally against SARS-CoV-2 turn against us?
Alarms go off: SARS-CoV-2 infection
Lets start by the beginning. Viruses are obligate parasites, which means they need to infect a cell to reproduce. This is because their genetic material (that kind of encyclopedia that contains all the information about a being) contains very little data. SARS-CoV-2, the cause of the pandemic that has infected more than 3.8 million people worldwide and caused more than 270,000 victims, is no exception..
To explain how a virus infects another living being, we could think of the operation of a key and a lock. The virus has on its surface a "molecular key"Able to open a"lock”Located in the cell and thus sneak inside.
Since practically the origin of the pandemic, and thanks to its resemblance to the entry mechanism in SARS-CoV-1 cells, it has been possible to know how this incursion occurs. We know that the "key" is the protein S on the surface of the virus, which binds to a receptor on the membrane of our cells (the "lock") called the angiotensin-converting enzyme (hACE2), which regulates blood pressure.
We also know that, once inside, the virus "hijacks" the engine room of our cells and forces it to work for its own benefit. In addition, the mechanism of virus entry into cells has recently been described in great detail, unlocking the keys to its infectivity and evasion of the immune system.
When defenses harm us
Every day we come into contact with potential infectious agents of a very diverse nature, from viruses and bacteria to fungi or helminths. Thanks to the response of our immune system, divided into innate and adaptive response, we can face them.
The innate immune system is responsible for quickly dealing with any possible pathogen with which we come into contact, regardless of its nature and in just 96 hours. Which, in many cases, is more than enough to eliminate the threat.
This innate immunity is mediated by soluble elements and cells such as Natural Killer or macrophages, the latter being responsible for the so-called "cytokine storm". Cytokines act as "messengers", aiding and coordinating the immune response. However, when they are produced excessively, cause the immune system to go haywire.
The problem is that these cytokines induce permeabilization of the walls of the blood vessels, allowing cells to pass into the tissues to fight infection. When they occur in an avalanche, the lungs fill with fluid, lower blood pressure, and cause thrombi to form.
An ace up the SARS-CoV-2 sleeve
Although previously we referred to the small size of the virus genome, SARS-CoV-2 contains approximately three times more information than an average virus (about 30kb vs. 10kb). In other words, his encyclopedia of life contains "extra pages" that give him some advantages.
One of those advantages has to do with another of the most important elements in the innate response: interferons. It is a family of soluble molecules that block the spread of viruses while preparing a more specific response. SARS-CoV-2 contains in that "extra information" genes, such as nsp1 or nsp3, capable of blocking the activity and production of type I and III interferons.
Furthermore, it has recently been described that the gene that encodes hACE2, that lock that the virus uses to infect our cells, is stimulated by interferon. In other words, the virus is able to partially disable our defense mechanisms and even take advantage of them to increase their ability to penetrate cells, transforming weakness into advantage. This has caused the use of interferon as a treatment to be currently in question.
Recovering an old friend from SARS-CoV-2
The data available to date seems to indicate that a poor response by interferons, as well as an excessive proinflammatory response, define the severity of the infection in COVID-19 patients.
Currently there are various treatments on the table whose objective is to help our immune system to act effectively against the virus. From antibodies that block cytokines like IL-6 (partly responsible for the cytokine storm), to antibodies that prevent the virus from entering cells. Treatment for SARS-CoV-2 may need to be recovered to the immune system for the cause.
(Article published by The Conversation)