August 22, 2026
Why the same virus can be mild for some and deadly for others
A burst of interferon-beta in the first 24 hours of a viral infection was closely linked to survival in mice and changed how immune cells responded
BySanjana Gajbhiye
Editor
Viral infections do not affect everyone in the same way. One person may recover quickly, while another becomes seriously ill, even when both face the same virus
Age, health, genes, and living conditions can affect how someone responds to a virus. Experiments in mice suggest that what happens during the first 24 hours of infection may also be important
A fast burst of an immune signal called interferon-beta was closely linked to survival. It also changed the behavior of neutrophils, immune cells that respond quickly when infection begins
Same virus, different outcomes
The team infected laboratory mice with a virus called VSV, which can cause a serious infection in mice. The mice had the same genes and lived in the same conditions, but some survived while others died
Researchers collected blood before infection and afterward, then looked back at the samples once they knew each mouse’s outcome
Associate Professor Tomohiko Okazaki of Hokkaido University helped lead the work and treated these natural differences as useful clues
“Biological variability should not always be viewed as experimental noise,” Okazaki said
Okazaki added that the team treated differences between genetically identical mice as useful biological clues rather than experimental noise
This approach helped them identify an early turning point in the immune response that might have been missed with more conventional comparisons
Early response to viral infection
The researchers looked at individual immune cells before and after infection. This helped them see how the body’s defenses changed over the next few days
One day after infection, the blood contained many more neutrophils. These fast-moving cells are among the immune system’s first responders and can swallow harmful material
Other immune cells temporarily became less common in the blood, while many cells switched on virus-fighting instructions. Most of these changes had faded by day five, showing that the response was strong but brief
Early interferon signals appeared to direct much of this activity. They warn cells about a virus and organize the body’s first line of defense
Signal linked to survival
The strongest interferon activity appeared in lymph nodes near the nose, with smaller changes in the lungs and spleen. The response peaked about one day after infection and then quickly decreased
Mice that survived had much higher blood levels of interferon-beta at the 24-hour mark
In one analysis, 23 mice survived for at least 14 days, while 33 died or had to be euthanized after severe weight loss
The team then blocked cells from receiving the interferon signal. Blocking the signal at the time of infection or one day later greatly reduced survival
Blocking the signal after two days had a much smaller effect. This showed that the timing of the early response was important
Interferon changed neutrophil behavior
The early immune signal changed how some neutrophils behaved. Some of these cells carried a protein called ICAM1 on their surface
Mice that died had more neutrophils without ICAM1, indicating that the balance between the two neutrophil populations may have mattered
Neutrophils carrying ICAM1 showed stronger signs of fighting the infection. They were also better at swallowing test particles
When researchers removed ICAM1 from these cells, fewer mice survived. This suggests that the protein helped the neutrophils protect the animals during infection
Bone marrow prepares cells
Neutrophils are made in bone marrow before they enter the blood. The researchers wanted to see whether the early immune signal changed these cells while they were still developing
When uninfected mice received interferon-beta, more neutrophils carrying ICAM1 appeared in the bone marrow as the dose increased. But after 24 hours, their numbers in the blood had not increased
Bone marrow from mice that later survived showed a stronger response to interferon-beta. The early immune signal may prepare neutrophils before they enter the blood
Researchers still do not know exactly how these cells protect the mice. They may clear more viral material, help other immune cells, or work in another way that was not measured
Timing could guide treatment
Okazaki connected the work to a wider question that became especially important during the COVID-19 pandemic
Why do some people become much sicker than others after catching the same virus, even when known risk factors do not fully explain the difference?
“Age and underlying medical conditions are well-known risk factors, but they do not fully explain this variability. Our findings identify an early immune mechanism that may help account for these differences and could inform future therapeutic strategies,” Okazaki said
The results do not mean that interferon-beta can protect people from severe viral infections
Its effects may depend on the virus, the dose, where it acts in the body, and when the response begins. A response that helps early could become harmful if it lasts too long
Human effects still need testing
The work used one virus in mice, so the same process may not happen during other viral infections or in humans
Human neutrophils can carry ICAM1 during inflammation, but researchers have not shown that these cells predict recovery or improve survival in people
Some parts of the analysis used only a few mice. The first comparison included two mice in each outcome group, while another cell comparison included three mice in each group
Larger follow-up experiments supported the main findings, but wider testing is still needed. Researchers must also learn what the ICAM1-carrying cells do and whether the same early signals appear in human infections
For now, the work shows that the immune system’s earliest moves can help shape a serious infection in mice, and similar signals might one day help doctors identify high-risk infections sooner
The study is published in the journal iScience
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