Why do you feel very weak after some viral infections?

Too much RNA can starve cells of energy, study finds

A new study by researchers has uncovered a previously unknown consequence of viral infection: Too much RNA inside a cell can disrupt its ability to produce energy.
Published in the journal Proceedings of the National Academy of Sciences, the study found that when excess RNA builds up inside cells during poxvirus infection, it can impair mitochondria—the structures responsible for generating most of a cell's energy—reducing the cell's ability to function normally.

The discovery could have broad implications for understanding viral infections, age-related diseases and RNA-based therapeutics, including mRNA vaccines, because excess RNA can accumulate in each of these conditions.
Scientists have long known that RNA degradation helps control protein production and remove defective RNA. This new study reveals another important role: It helps cells maintain the energy they need to function properly.
The findings suggest that RNA degradation serves a broader purpose than scientists once realized. In addition to controlling protein production, supporting RNA quality control and helping cells regulate immune responses, it also helps protect the cell's ability to generate energy.

RNA exists in many forms. Messenger RNA (mRNA) carries the genetic instructions cells use to make proteins, which help cells perform their normal functions. Another form, double-stranded RNA (dsRNA), is commonly produced during viral infections and alerts the immune system that something is wrong.

During viral infection, viruses can produce large amounts of RNA. If cells cannot break down the excess RNA quickly enough, the buildup can damage mitochondria and reduce the cell's ability to generate energy.

While scientists already knew that excess dsRNA can trigger immune responses and that cells need to control dsRNA levels, the effects of mRNA came as a surprise.

mRNA is a normal component of our cells, but it seems like with many good things, if we get too much, that can become a problem for the cell. When too much RNA builds up, including mRNA, it can damage the mitochondria and interfere with the cell's ability to produce energy.
Viruses rely entirely on host cells for energy and protein production, but producing too much viral RNA can overwhelm the very cells viruses depend on to survive.
poxviruses—the family of viruses that includes smallpox and mpox—appear to use RNA cleanup systems to degrade RNAs and keep infected cells functioning long enough for the virus to continue replicating.

If the cell is not healthy, the virus would not replicate well. The virus needs to keep RNA levels balanced inside the cell.
The team also found that mitochondrial impairment occurred before major immune responses were activated and did not depend on the immune system's usual response to infection, further supporting the idea that RNA itself contributes to the damage.
Researchers think the negatively charged RNA may accumulate around mitochondria and disrupt the electrical balance needed for energy production, although how it happens is unknown.

The findings may also have implications beyond viral infections.

Researchers have observed RNA accumulation in a variety of conditions—including some cancers, neurodegenerative diseases and age-related disorders—suggesting that mitochondrial damage may be one way excess RNA contributes to those conditions.

Perturbation of RNA homeostasis impairs mitochondrial respiration during poxvirus infection through excess RNA accumulation, Proceedings of the National Academy of Sciences (2026). DOI: 10.1073/pnas.26051941