The conflict between cellular and viral organisms has been the major engine of biological evolution. ~ French molecular biologist Patrick Forterre
A primary driver of evolution has been the eternal pestilence of cells everywhere: viruses. Virus success in surviving, replicating, and spreading depends upon productive interaction with many cell components. These host dependency factors are proteins that a cell requires for normal functioning but are hijacked by a virus to suit its needs.
Another class of cellular components which interact with viruses are restriction factors: cell proteins which play no obvious role in normal functioning, but seemingly exist solely to interfere with a virus’ life cycle. Many restriction factor proteins are encoded by genes whose expression is induced by interferons: proteins produced in response to the presence of abnormalities, including viruses, bacteria, and tumors.
All life must survive their corresponding viruses. Thus, antiviral systems are essential in all living organisms. ~ American virologist Luis Villarreal
Detecting a virus results in a cascade of genetically scripted responses. First comes interferon manufacture, followed by unleashing restriction factors.
All viruses recognize their cellular hosts by binding to specific molecules on the cell’s surface, typically a specific glycoprotein. This binding site is called a receptor by virologists; a term off-putting to biologists, as a cell plays no active role in inviting infection by sporting viral reception sites.
To a virus, the receptor provides an appropriate attachment point as well as telling the virus that it has come to the right place to invade the cell membrane and initiate its enterprise. The virus-binding region of a receptor is often unrelated to the receptor’s normal function. Generally, surface receptors act as an interface for cellular operations, including intercellular communication.
Virus evolves a mechanism to persist, cells evolve a way to defeat that mechanism, virus evolves a way to defeat what the cell just evolved. ~ American virologist Rob Kalejta
Cells evolve resistance to viral infection by altering amino acids in the binding site without disturbing the part of the receptor critical to proper functioning. This highly specific molecular tweaking comes via intelligent genetic adaptation: either epigenetically or by altering DNA coding sequences as necessary.
The genes that script the production of proteins involved in normal functions resist mutations by removing errors in DNA replication. In contrast, genes encoding restriction factors rapidly adapt. They must, as viruses are constantly evolving to evade restriction factors.
Viruses quickly adapt to changes in their binding sites. Some, such as HIV, figure out how to inactivate restriction factors. This creates an intense cycle of competitive coevolution at the molecular level between a virus and its host cell.
In contrast to the sometimes rapidly revolving adaptations in restriction factors, host dependency factors seldom change. That is because viruses and cells employ host dependency factors in the same way, for the same functionality.
A cell relies upon host dependency factors for its own operations. It cannot afford to alter these important proteins to thwart viruses. Hence, the genes of host dependency factors are conserved.
Spiraling virus and host cell coevolution adds to the virus’ knowledge base, yielding greater flexibility in recognizing receptors. This invaluable education can graduate a virus to the next level: learning how to hop from one species to another.