Mon. Oct 2nd, 2023
It is still a mystery why some people are immune to diseases that can cause death in other people. This was what we saw over and over when COVID-19 was a pandemic.

Every family is affected by illness. Superspreaders are events that infect many people. However, some lucky people often escape with good health. Is it possible that the virus did not enter your body? Is it possible that some people have an inherent immunity to pathogens they have not encountered before?

The resistance to infection is not just an academic curiosity. Understanding the mechanisms behind it could help you prevent future outbreaks.

Andras Spaan MD, a microbiologist at The Rockefeller University, New York, says, “If we could identify what makes some people resist, that immediately opens avenues to therapy that we can apply to all those people who have the disease.” City of New York.

Spain is part of an international effort to find genetic differences that prevent people from getting infected with SARS-CoV-2, the virus that causes COVID-19.

Research is focusing more on the causes of infections and less on how to resist them. A few researchers are still trying to figure out how to fight some of the most deadly and common diseases. Some of their findings have been incorporated into treatments.

The most striking example of how foreign genetics can trigger treatments to help many comes from studies on the human immunodeficiency virus (HIV), the virus that causes an immunodeficiency disorder. acquired (AIDS).

A genetic quirk

Multiple research groups discovered in the mid-1990s a mutation in the gene CCR5 which conferred immunity to HIV-infected people.

It codes for the protein that is found on the surface of white blood cells and aids in the circulation of immune cells fighting infection. HIV uses CCR5 to infiltrate white blood cells and enter infected ones.

This mutation is also known as the delta 32. It reduces the length of the protein and makes it difficult to penetrate the outer layers of cells. The CCR5 gene is found in 2 copies in people who have the delta 32 variant. They do not have any CCR5 proteins on their outer layers of white blood cells. However, they had never been infected. There were only 2 copies of CCR5 Delta 32 among the more than 700 HIV-positive people. CCR5 delta 32..

This knowledge was used by pharmaceutical companies to develop drugs that block CCR5 and slow down the progression of AIDS. HIV patients were approved to use maraviroc, which is a drug maraviroc that Pfizer sells.

This type of genetically determined, total, innate immunity to infection has been seen in a few cases. Each one involves cell-surface molecules thought to aid a pathogen or virus in getting into cells.

Locking Out Illness
“Intracellular pathogens must first enter the cells,” Murphy says. Murphy says that if the virus doesn’t reach the door, it can’t complete its first step in its lifecycle.” “Getting inside is essential.”

Cell surface molecules can change, which could increase your risk of getting an infection or other serious illness. Blood group histogens are one of the cell surface molecules that can be associated with increased or decreased risk of various infections. These blood-related molecules, also known as types A and B, are the most commonly used members of this group.

Scientists also discovered a case where these molecules are immune to infection. Researchers discovered that individuals who possess a functional copy of FUT2 (the gene that encodes the virus) are immune to the Norwalk virus. This virus is a group of over 30 viruses that causes diseases in the digestive tract. .

The FUT2 gene encodes an antigen that detects blood group members in saliva, blood fluids, and red blood cells.
Lisa Lindesmith, University of North Carolina Chapel Hill virologist, says that no matter how many virus particles were given to an individual if they don’t have the first enzyme, they won’t be infected.

No Norovirus

Norwalk, a rare norovirus strain, is very rare. FUT2 deficiencies provide protection against common norovirus strains such as GII.4, which have been steadily spreading around the globe over the past quarter century. Children in developing countries are most affected by these infections, which can cause malnutrition and contribute to child and infant death.

The process of translating genetic resistance discoveries into drugs or other substances that reduce or eliminate noroviruses’ impact is slow.

Lindesmith adds that the biggest obstacle is the inability to study the virus without humans.

Noroviruses can be difficult to propagate in the lab “and there is not a small animal model of gastrointestinal disease caused primarily by viruses.”
Lindesmith states that we are clearly making great strides in developing these skills. “But we are just not there yet.”

Before COVID-19 was discovered tuberculosis (also known as TB) was the leading cause of death worldwide each year. It is caused by Mycobacterium tuberculosis (a bacterium that causes lung disease). This has been a major cause of death for many years.

Approximately 85% to 95% of people with healthy immune systems who have TB are able to manage the disease and never get active lung disease. People who are exposed to microbes via aerosols or droplets more often than patients with active lung diseases do not get infected.

Thwarting Tuberculosis

Understanding the causes of different types of resistance can help us find cures, vaccines, and other ways to fight tuberculosis. Elouise Kroon MD, a doctoral student at the University of Stellenbosch in Cape Town (South Africa).

She says that the lack of a gold standard to measure infection makes it difficult to study. “So we infer infection using two types of tests,” she says. The skin test is one, and the blood test determines the immune response to the different bacteria molecules.
Kroon and others studied resistance to infection in people living in high-risk areas or in their households. These studies do not use the exact same definition of “resistants”, nor do they accurately record people’s exposures or monitor long-term to ensure that people are positive.

Marlo Moller (Ph.D., associate professor at Stellenbosch University’s Tuberculosis Host Genetics Research Group) says that the most reliable evidence from research to date is that it links resistance against infection to certain variations in immune molecules, as mentioned in HLA-class II antigens.

“This always seems to be everywhere. He adds that the rest of the picture isn’t so obvious. Many studies have not found the same thing. It is different in different people,” this could be due to the long evolution of humans and TB, as well as the fact that there are many varieties of bacteria in different parts of the world.

COVID-19, a relatively new infection, has caused severe illness in some people. It is difficult to understand what causes it and how to resist it.

Overcoming COVID

The pandemic research by COVID Human Genetic Effort began in the early stages. Spaan was a member of the global consortium that linked severe COVID-19 to a deficiency in immune-related molecules.

Different studies have looked at resistance to COVID-19 infection. Type O blood seems to be more susceptible to the virus.

But, studies to date have focused on the most common genetic variants that are likely to have little resistance. Genetics researchers are beginning an effort to identify genes that can have an impact even if they are extremely rare.
 This group seeks out those who are not affected by COVID-19 despite prolonged exposure. It is difficult to determine if a person has been infected with the virus, similar to tuberculosis. However, the team uses blood tests to find those most likely to be healthy.

 They plan to examine the genomes of people to determine what factors affect the risk of infection. Then, they will conduct lab studies to discover the mechanism of resistance.Spain claims that its research was inspired in part by earlier efforts to find the inborn immunity to infections. Prior attempts at rapid sequencing technology were made at “a different time” Spaan states.

“Now, we have the modern technology to make this happen more efficiently. 

Research is now more difficult due to the emergence of viral variants like Omicron COVID types and Delta COVID varieties.“These new variants of COVID have made it even more urgent to discover and unravel the inborn resistance mechanisms to COVID. We also anticipate that COVID will be with us for many years.” 

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