Brazilian woman discovers how the Covid-19 virus tricks the immune system

Why does the coronavirus manage to circumvent the immunity of some individuals, including healthy ones, wreaking havoc, hospitalizations and even deaths? This question gained personal contours for the scientist Marcella Regina Cardoso. In 2021, when vaccines were not available in Brazil, the biologist, who was already working in Harvard Universityin the USA, lost his father to the disease.

Pain and scientific flair instigated Marcella to ask for authorization from the prestigious American institution to lead a line of research into the possible mechanisms used by the SARS-CoV-2 to escape the organization’s security forces. Years of dedication from the Ph.D., who until then had been studying the potential of immunotherapy against breast cancer, yielded surprisingly significant results.

Marcella and the Harvard team, in partnership with State University of Campinas (Unicamp), uncovered a pathway orchestrated by the Covid-19 virus to trick our immune system and succeed in infection and viral replication. The findings have just been published in the academic journal cellone of the three journals with the greatest impact on the planet, alongside Nature It is Science.

“After my father died, I thought: why not use my intellectual background, creative capacity and critical sense to make a difference in this story?”, says the scientist, graduated from UFSCar and with a master’s degree and doctorate from Unicamp. Marcella pored over a panel of genomic and molecular data on the Covid-19 agent until she noticed a precious clue.

“We identified an accessory protein of the coronavirus that allows it to escape defense cells known as natural killers (NK), the natural killers, who are on the front line of immunity”, summarizes the author of the work.

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Evolutionary stratagem

When a viral invasion, infected cells tend to express, on their surface, proteins that signal to the organism that there is something wrong there. These are MIC-A and MIC-B, two snitches that attract the attention of our immune army. By identifying these proteins, NK units are recruited to the cells taken over by the virus and attack them, in a rush to stop the infection.

This is how things are expected to work. It turns out that Sars-CoV-2 has an ace up its sleeve to circumvent this operation. “It has an accessory protein, ORF6, which, when the virus opens inside the cell, goes to the MICs and sweeps them from there”, explains Marcella. “With this, the natural killers They cannot recognize the infected cell and cannot fight the infection.”

The discovery came to light after a series of experiments, involving mapping of viral genes and proteins, analysis of samples from patients with Covid-19, most of which came from Brazil, and tests with lung cells and mice. “Evaluating patients’ serum helped us understand the association between the immune response and the outcomes of those people sickened by Covid-19”, says Marcella.

The data obtained suggests that, despite the variant, the coronavirus uses this mechanism to evade immunity. Something that only reinforces the importance of vaccinationwhich provides support to the human body to mount a defense response to the pathogen.

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Valuable information

The results of the research published in cell pave the way for an understanding of how viruses with pandemic potential, such as coronaviruses, learned to evolve to evade the mammalian immune system. This is a relevant finding to search for new therapeutic targets or ways to interrupt the infectious cascade.

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“And that becomes more important if we think that everything leads us to believe that we will face new pandemics”, says Marcella.

The Harvard group has even gone a step further, at least with regard to Sars-CoV-2. “Based on the tests carried out, we realized that there is a monoclonal antibody, a drug in pre-clinical phase, which manages to disable this virus escape route”, reveals Marcella. “It binds to the MIC proteins and prevents ORF6 from being able to get them out.”

The medicine is in the experimental phase, but perhaps it offers a way out to prevent higher-risk infected patients from getting worse when hospitalized. This is still one of the “pains” of Covid-19, even though vaccination reduces the chances of danger.

Ultimately, knowing, in molecular detail, how the virus can deceive us is crucial to knowing how to control it once and for all.