Cells from serodiscordant couples were analyzed, in which cases the women were resistant
During the Covid-19 pandemic, a fact intrigued health professional Maria Tereza Malheiros Sapienza. Her husband, doctor Marcelo Sapienza, was infected twice with SARS-CoV-2 –once in April 2020 and another in January 2022–, but she did not show any symptoms of the disease despite being in direct contact with her partner both times. occasions.
Curiosity about the case was not exclusive to the couple, who became part of research conducted at the (Center for Human Genome and Stem Cell Studies) – a Center for Research, Innovation and Diffusion () of Fapesp based at USP (University of São Paulo) – about “pares sorodiscordantes”as cases were called in which only one of the partners was infected and the other remained asymptomatic, despite sharing the same bed without the use of special protection.
The work analyzed the genetic material of 86 couples, of which only 6 (among them Maria Tereza and Marcelo) remained serodiscordant throughout the pandemic, with one of the partners becoming infected more than once. Interestingly, in the 6 cases, only women remained resistant to SARS-CoV-2. The results were in the magazine Frontiers in Cellular and Infection Microbiology.
From the analysis of blood cells from these couples in experiments in vitroresearchers found that women resistant to the virus had increased expression of the gene IFIT3 (acronym in English for interferon-induced protein with tetratricoptide repeats 3) compared to their husbands. The expression of this same gene among women who acquired symptomatic infections was low, similar to that of the group of husbands.
“It is a gene that is part of the antiviral response. It has already been described in previous studies as being related to protection against other viral diseases, including dengue, hepatitis B and adenovirus. However, in our work, we managed for the first time to prove this protective effect beyond theory, as it is very unlikely that the 6 women were not exposed to SARS-CoV-2 in a condition in which they shared environments and cared for their infected husbands.”said , 1st author of the article, the result of his post-doctoral project at Fapesp.
As the researcher explains, the gene IFIT3 it encodes a protein of the same name that binds to the virus’s RNA, making it impossible to replicate and preventing the pathogen from invading new cells and the disease from progressing.
“The virus invades the cell, however, the entire process of replicating itself to break the cell membrane and invade as many other cells as possible is interrupted right from the beginning. The IFIT3 protein ‘sticks’ to the viral RNA, making its replication impossible. In other words, it’s not that these women weren’t infected, they were. But the virus barely multiplied inside their cells and, therefore, they did not have the disease.”these.
New research target against covid
The study with serodiscordant couples began in 2020, the beginning of the pandemic in Brazil. In the 1st phase, the researchers analyzed the exome – part of the genome where the protein-coding genes are located – of 86 couples and noticed that there was a difference in 2 genes between the resistant and infected partners. These variants apparently decreased NK cells (natural killers), one of the types of lymphocytes, only in infected partners.
Throughout the pandemic, there were several cases of reinfection in the group of research volunteers, with 6 six women remaining resistant. To investigate the protection mechanism, the researchers analyzed blood samples from these couples on two occasions: one in 2020, shortly after the men’s first infection, and another in 2022, after the second infection (it is worth noting that on this second occasion the participants had already had received two doses of the covid-19 vaccine).
“With these samples, we isolated peripheral blood mononuclear cells, mainly lymphocytes and monocytes, and stimulated them in the laboratory with a synthetic viral agent that mimics SARS-CoV-2. With this experiment, we were able to notice that cells from resistant women showed increased expression of the IFIT3 gene compared to both their husbands and a group of five women who developed Covid-19. [grupo-controle]”says Vidigal.
In addition to responding to an old curiosity since the first months of the pandemic, the study brings important developments. The finding makes the IFIT3 a potential therapeutic target for new antiviral therapies, which could supposedly enhance the innate immune response against SARS-CoV-2 and other pathogens – since the protection conferred by overexpression of this gene is not exclusive against SARS-CoV-2.
“Without a doubt, the great result of this research is that we found a biomarker of resistance to the virus. The study design allows us to be almost certain that women were exposed to the virus and showed resistance. We also reproduce in the laboratory what may have happened in your cells when they came into contact with SARS-CoV-2.”says , professor at the Faculty of Medicine (FM-USP) and researcher at InCor (Instituto do Coração).
“But they still needus to delve deeper into the biology of resistance, understanding which mechanisms lead to greater expression of the IFIT3for example. Therefore, despite having this important finding, our study continues with even more questions”adds Cunha Neto.
The article Potential protective role of interferon- induced protein with tetratricopeptide repeats 3 (IFIT3) in COVID-19 can be read.
With information from .
