Why the same virus affects people differently, triggers varied outcomes

A new study shows that both our genes and life experiences leave lasting epigenetic marks on immune cells, shaping how differently we respond to the same virus

Why does the same virus cause mild illness in some people but severe disease in others? Scientists now say the answer lies in a mix of inherited genes and life experiences.

 

According to a study titled Genetics and environment distinctively shape the human immune cell epigenome, published in Nature Genetics, both genes and life experiences leave lasting epigenetic marks on immune cells, shaping how the body responds to infections from Sars-CoV-2, HIV and influenza viruses.

What did the study find?

Researchers at the Salk Institute, California, created a detailed map of the human immune cell epigenome, which is a collection of chemical tags that regulate gene activity without altering the DNA code itself.

 

 

By analysing 171 blood samples from 110 individuals exposed to infections such as HIV-1, influenza, Sars-CoV-2, MRSA, and even environmental chemicals like organophosphate pesticides, the team identified two major types of epigenetic changes. These changes, unlike genetic changes (mutations), are reversible and do not change the sequence of DNA bases, but they can change how your body reads a DNA sequence. The two epigenetic changes identified by the researchers under this study were:

• Exposure-associated changes (eDMRs) driven by infections or environmental factors
• Genotype-associated changes (gDMRs) linked to inherited genetic variation

They found that these two forces shape immune cells in fundamentally different ways.

 

According to the researchers, every cell in your body contains the same DNA. Yet a T cell behaves very differently from a type of white blood cells called monocyte, which is an essential fighter in the immune system as it finds and destroys germs. That is because of epigenetic markers, chemical modifications such as DNA methylation that switch genes on or off.

 

Unlike the genetic code, which is largely fixed at birth, the epigenome is dynamic. It can change in response to infections, vaccines, pollutants, diet, stress and other life experiences. The study shows that these changes leave lasting imprints on immune cells.

 

Using advanced single-cell methylation sequencing and chromatin accessibility profiling, researchers were able to map epigenetic changes in specific immune cell types, rather than analysing mixed bulk samples.

 

They discovered that

• Genetic influences (gDMRs) tend to cluster within gene bodies and are more stable, particularly in long-lived memory immune cells. Thus, your genes set the foundation.
• Experience-driven changes (eDMRs) are enriched in regulatory regions such as enhancers and promoters, areas that help control how genes respond to threats. In simple terms, your life experiences fine-tune the response.

The researchers found that specific infections leave distinct epigenetic signatures in immune cells. Here's what the researchers found about some specific infections like Sars-CoV-2 and HIV:

• HIV-1 infection remodelled DNA methylation and chromatin accessibility, particularly in memory T cells.
• Sars-CoV-2–associated changes were especially pronounced in monocytes and naïve T cells.
• Severe Covid-19 cases showed different epigenetic patterns compared to non-severe cases.
• Individuals of African genetic ancestry showed stronger methylation effects in certain infections, consistent with observed disparities in disease severity.

These findings suggest that immune responses are shaped not just by the pathogen, but by the biological history written into immune cells.

Why does this study matter?

As we saw during the Covid-19 pandemic, two people can encounter the same virus and experience radically different illnesses. This study suggests the answer lies in a layered interaction between inherited genes and accumulated life experiences, etched into immune cells through epigenetic marks.

 

The researchers highlighted that your immune system is not just a product of your DNA, it is also a living record of everywhere you have been and everything you have encountered, and decoding that record may be key to predicting, and improving human health in the future.