Viruses that imitate human proteins may be more common than previously assumed

By imitation of host protein, viruses can usually react immune, but sometimes trigger this autoimmunity.

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DIssing between self and non-self-self is a critical ability of the immune system. Some pathogens have developed proteins that resemble those of their host, a mechanism called Molecular Mimikry to avoid this surveillance system. However, immune training is not perfect, so do innovations that recognize self -proteins occasionally into the milieu. Your presence does not immediately increase alarms, but if a pathogen with the same protein penetrates the body, it can trigger an immune response against the same sequence on the body's own cells.

Previous work on molecular mimicry focused on the 3D structure of proteins, which is important for the antibody-mediated immune recognition, but T cells typically recognize short linear peptide sequences.¹ Studies on the mimicry in these short sequences often concentrate on a subgroup of viruses or presumed proteins.^2.3 Researchers have now carried out a more comprehensive analysis in which more than 100 human infected viruses are examined on Mimikry in short linear peptide sequences.⁴ They showed that this phenomenon is widespread throughout the virom. These results, published in Natural communicationCould help researchers to explore new autoimmune triggers and potential interventions.

Esther Melamed, doctor scientist and neuroimmunologist at the University of Texas in Austin, and her group examine how the molecular mimicry affects the development of autoimmune diseases. A group in particular is multiple sclerosis (MS), which has a strong connection with the Epstein Barr virus (EBV).⁵ Melamed said her team was interested in examining the contribution of other viruses.

When Covid-19 pandemic compulsion its group to work from home, she introduced a perfect opportunity to explore this question because these sequences are available online. Cole Maguire, a doctoral student of the neurosciences in Melamed's group, first examined the Sars-Cov-2 virus for molecular mimicry. “As soon as we got it out, we say:” Well, what if we just let it run for every virus, “he said.

“We don't necessarily know why viruses win [mimicry] And what advantages you have by winning it, “said Maguire.

Using consensus sequences from 134 human infected viruses and the commented human genome, the team searched for linear sequences of eight, 12 or 18 amino acid residues, which had no more than three misconducts in these epitopes. They found that viruses from the same family and that viruses that cause chronic infections showed more imitators than viruses that cause acute infections. Two families, Herpesviridae And Knocking viridaeIncluding viruses such as herpes simplex virus 1 and MPOX, some of the highest rates of molecular mimicry.

“Even if you look at other autoimmune diseases [beyond MS]They are really connected to a variety of herpes viruses. So it was interesting to see this trend at a family level, as this could indicate a reason why herpes viruses are often associated with autoimmunity, ”said Maguire.

“We really wanted to examine the biological effects and try to find out how molecular mimicry fits the human body as a whole,” said Melamed. For this purpose, the team analyzed the paths from which these proteins came, and found that many were involved in cellular replication and inflammation, but there was no preference for a specific cell or a specific type of fabric.

Then they examined which chromosomes coded the imitated proteins. “One of the most interesting things for us was that viruses, when we looked at chromosomes in the entire genome, tended to avoid that proteins were imitated on the Y chromosome,” said Melamed, adding that this finding could indicate evolutionary pressure on the virus to face more universal proteins.

Since the T-Zell immune training occurs against self-proteins in the thymus, the team compared the genes of the viral proteins with the sequences expressed by thymus cells. They observed a large overlap of virus sequences and those of thymus gene.

Although MS has traditionally been characterized as a T -Zell -mediated disturbance, B cells have recently contributed to autoimmune disease.⁶ The team examined the prevalence of MS car antibodies on peptide sequences that are imitated by EBV. They showed that the majority of the most common MS autoantibodies contained an eight-side sequence that agreed with an EBV sequence. “EBV actually plays a major role for the existing antibodies to contribute to the production of these antibodies,” said Melamed.

Ana Beatriz Depaula-Silva, immunologist at the University of Utah, who examines how viral infections contribute to neurological disorders and not involved in the study, said it would be important to pursue this work with functional studies in order to determine whether all subsequent channels play a role in developing autoimmune diseases. However, she said that it was interesting to see the extent of the mimicry in viruses. “It brings a lot to the field,” she said.

“I think the extent of what we found was that there are so many chronic viruses that can lead to molecular mimicry that there is a bigger problem that we don't really think about when we see patients clinically with autoimmune diseases,” said Melamed.