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When Influenza Attacks, It Causes A Cellular Coup d'État

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Although flu season has yet to begin in Canada, the threat is looming. Temperatures are dropping and soon, the virus will make its annual appearance. When this happens, hundreds of thousands will be infected with over 12 thousand requiring hospitalization and sadly, over three thousand succumbing to illness.

Most people are familiar with the symptoms of the flu. It's a real knock down of the body with a combination of fever, cough, fatigue, and loss of appetite. These arise as a result of the battle our immune systems are engaging against the virus. Typically, the infection lasts for about a week to ten days with about a week of recovery.

While we may be aware of the outwardly effects of the infection, researchers have been trying to learn about what happens at the microscopic level inside the cell. Much like any viral infection, the invasion leads to a shutdown of normal processes as the virus uses up all the nutrients and resources to make more copies. Yet the mechanism of this takeover has been for the most part a mystery.

That may change as a group of Israeli researchers have provided a glimpse at how influenza takes over the cell. Their results reveal what may be best described not as a hijacking but instead as a cellular coup d'état. This takeover can have drastic consequences for the cell but also may explain why it is so difficult to control the infection once it has begun.

The team worked with lab cultures so they could examine the invasion at the molecular level. The cells were at first infected with the virus and then over time, examined for any changes in the way the cell lives. This meant examining the genetic material, the cellular coding device for ensuring proper health, messenger RNA, or mRNA, and proteins responsible for decoding mRNA, ribosomes. This approach allowed the group to understand exactly how the cell is attacked by the virus.

When the results came back, the group were shocked at the ferocity of the assault. Of the over 7,000 different types of mRNA in the cell, none were left unaffected. Their numbers dropped across the board. By eight hours after infection, over half of the mRNAs in the cell were viral. This meant the normal process of cellular life was hampered almost immediately.

Even as the cell was trying to kill itself, the virus maintained one of the critical components for its own life and replication.

What was truly surprising was the type of cellular mRNA most affected. Those responsible for coding cellular repair and maintaining business as usual were the most severely affected. On the other hand, those responsible for keeping the cell alive were not stopped. This meant the virus had taken over the cellular territory but kept the main functions of life. In essence, this was not a killing action. It was a coup.

Because of this particular observation, the team wondered if the virus had figured out a way to protect its most important member -- the viral genome -- from becoming caught up in the battle. They were able to find that protection although it came in the form of a very unlikely source. Instead of having specialized bodyguard proteins, the virus used ribosomes. This level of ingenuity was surprising but made perfect sense. The one protein needed to ensure both the cell and virus could function properly -- thus be immune to either attack -- was also the perfect choice to keep the most integral part of the virus safe.

As for the cells, the researchers found they put up a fight. Within the first few hours of the attack, a stress response was seen. Known as Eukaryotic Initiation Factor 2α (eIF2α) phosphorylation,, this biochemical action relates key information to the nucleus. In turn, the nucleus begins to produce defensive proteins that help fight the virus and signal the immune system outside the cell. Yet by eight hours, this process was also shut down. The cells tried to stop the coup but inevitably failed.

There was one final insult to injury. Normally, when a cell is facing death, regardless of the cause, it will shut down the energy production facility, the mitochondria. Yet, the researchers saw no damage to this critical organelle. Even as the cell was trying to kill itself, the virus maintained one of the critical components for its own life and replication.

There was one part of the process missing from this work. The authors could not convey the overall effect this coup has on an individual. The events described here only represent one cell. Yet when we are infected, there could be millions or more of these individual coups occurring in the lungs. This widespread takeover can lead to lung damage both from the virus and also from the immune system. After all, it will be late for the battle and may choose to wipe out the area with toxic chemicals rather than trying to fight the viruses individually.

Taken together, the results of this study reveal the importance of prevention during flu season. People may choose to more closely adhere to hygiene, opt to get vaccinated, or move to an unaffected region of the world. Regardless of the approach, the key is to be sure the virus doesn't get into the lungs. It's the only effective way to thwart the viral coup and its consequences.

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