Many common viruses rely on hijacking your cell’s mitochondria in order to replicate and thrive. Others indirectly cause mitochondrial damage in order to survive.

With exquisite execution, viruses have developed tactics akin to a well-planned siege. Espionage, blitzkrieg, intracellular mutiny…viruses are often victorious, causing long-term problems for the host. Life-long infection, persistent reactivation, and cancer promotion are all well-established consequences of viral infection.

1. Calcium Depot Hijack

Maintaining calcium balance is essential for all cell types to function properly. From muscle cell contraction to nerve cell firing, calcium concentrations must be stable to allow for proper communication between cells. For some viruses to survive, they must utilize our calcium stores during different stages of the virus lifecycle, thus throwing off normal calcium balance.  

For example, the Hepatitis C virus over time targets the mitochondria by prompting an influx of calcium. Excessive calcium influx disrupts normal mitochondrial function and triggers mitochondrial death. This may be a primary means in which chronic Hepatitis C virus leads to cirrhosis of the liver and liver failure.

Similarly, Rotavirus disrupts calcium balance by depleting stores. This other extreme also leads to problems for the mitochondria and the entire cell. Too little calcium makes the cell membrane structurally vulnerable, with eventual cell death through rupture or lysis.

2. Intracellular Mutiny

Many viruses induce the generation of free radicals (unstable molecules with unpaired electrons) to indirectly help them survive in the host cell. Within the cell, mitochondria are especially vulnerable to increasing oxidative stress; which can overwhelm their protective mechanisms. An onslaught of free radicals damages the mitochondrial membrane making it “leaky” and subject to complete rupture.

Some viruses, like Epstein-Barre, utilize the intracellular chaos of free radicals, to thrive. Within 48 hours, EBV hijacks the cell and initiates free radicals. Latent infection can be reactivated by continued oxidative stress. These radicals activate viral genes in EBV which signal virions to bud from the cell and reactivate the infection.

Mitochondrial Servitude

Viruses take complete charge of the cell by dictating where the mitochondria should be distributed. Because they thrive on oxidative stress and require an ample supply of ATP, viruses can move mitochondria near the viral replication factories.

In HIV-1 and Hepatitis B virus, proteins are made that string together a tubule network which pulls the cell’s mitochondria toward the viral replication centers. In a cellular tug-of-war, mitochondria are densely clustered around the viral factories. They then are indentured to churn out ATP and free radicals for the viral factories at the expense of the rest of the cell.

Mitochondrial Scout Takedown

The membrane of your mitochondria is home to signaling proteins that detect viruses, called MAVS. MAVS sound the alarm at the sign of viral infection, which triggers the cell to begin the cascade of defense mechanisms. Upon detection, MAVS trigger the release of interferon—the cell’s strongest weapon against viruses.

Some viruses are known to completely take out MAVS from the mitochondrial membrane. MAVS are cleaved from the mitochondrial membrane and left free-floating in the cell.  Like a battalion that’s lost its lookout, the cell is vulnerable to a quick viral attack.

Viral Espionage

Like a clever spy, viruses are known to mimic cellular and mitochondrial proteins to survive. Mimicking the host proteins allows the viruses to have an insider that can dictate all cell functions to the viruses’ advantage.

At the mitochondria, proteins commandeered by viruses dictate what types of proteins are made and where those packages go in the cell. The viral contraband is stockpiled within the cell, or the mitochondria, where it promotes viral replication.

As an example, HIV-1 hijacks mitochondrial proteins leading to permeability of the mitochondria and easy release of packages needed for the HIV virions. Other viruses, such as adenovirus, can mimic mitochondrial proteins and enter the cell’s nucleus without detection of antiviral defenses.

References

Anand SK & Tikoo SK. Viruses as modulators of mitochondrial functions. Adv Virol. 2013;2013:738794. http://www.ncbi.nlm.nih.gov/pubmed/24260034