A virus is a segment of genetic material, either DNA or RNA, enclosed in a protein shell. Its objective is to enter a host and use the host’s cellular machinery to replicate. During this rapid replication, the virus’s genetic code can undergo changes, known as mutations.
How Viral Replication Leads to Mutations
To replicate, a virus hijacks a host cell, turning it into a factory for producing new viral particles. This process involves copying the virus’s genetic blueprint at high speed. Similar to a photocopier making rapid duplicates, this replication is not always perfect, and errors can be introduced into the genetic sequence, causing mutations.
The frequency of mutations depends on the virus’s genetic material. DNA viruses have lower mutation rates because they use the host cell’s replication enzymes, which include proofreading mechanisms that can detect and correct errors.
In contrast, RNA viruses like influenza and COVID-19 have much higher mutation rates. Their replication is managed by an enzyme, RNA-dependent RNA polymerase, which lacks a proofreading function. This absence of error correction leads to a mutation rate that can be 100 to 10,000 times higher than that of DNA viruses.
Natural Selection and Viral Adaptation
The constant introduction of mutations creates a diverse swarm of slightly different genetic versions of a virus. Most of these mutations are neutral or detrimental, harming the virus’s ability to replicate. These less-fit versions are quickly eliminated from the population.
Occasionally, a mutation provides an advantage. If a random mutation helps a virus replicate more efficiently, spread more easily, or evade the host’s immune system, that viral variant will have a higher chance of survival. Over time, this advantageous variant can outcompete others and become the dominant version.
This process is influenced by selective pressures from the host population. For instance, as more people gain immunity through infection or vaccination, there is a selective pressure favoring mutations that can bypass this protection. A virus that can infect previously protected individuals has a survival advantage, driving the evolution of new variants.
Impact of Mutations on Viral Behavior
Mutations can alter a virus’s characteristics, such as its transmissibility. For example, the N501Y mutation, found in several SARS-CoV-2 variants, enhanced the virus’s ability to bind to human cells. This contributed to its increased spread.
Mutations can also affect disease severity, making a virus either more or less dangerous. The Delta variant of SARS-CoV-2 was associated with an increased risk of hospitalization, indicating a rise in severity. Conversely, some viruses evolve to cause milder illness, which can aid their spread by allowing infected individuals to remain active.
Another consequence is immune evasion. Mutations in the surface proteins that the immune system recognizes can make a virus harder for antibodies to neutralize. The E484K mutation in some SARS-CoV-2 variants, for example, was linked to reduced antibody effectiveness. This is also why the influenza vaccine is updated annually to account for mutations in the flu virus’s surface proteins.
Monitoring Viral Changes
To track evolutionary changes, scientists use genomic sequencing to read the complete genetic sequence of virus samples from infected individuals. By comparing new samples to older ones, researchers can identify mutations as they arise and monitor their spread in near real-time.
This global surveillance data is shared through international databases. Based on this information, organizations like the World Health Organization (WHO) classify emerging variants. A variant may be labeled a “Variant of Interest” (VOI) if it has genetic changes predicted to affect its behavior and is causing localized outbreaks.
If a variant demonstrates increased transmissibility, causes more severe disease, or evades vaccines or treatments, it may be elevated to a “Variant of Concern” (VOC). This classification system helps public health officials make decisions, such as:
- Updating public health recommendations
- Adapting diagnostic tests
- Guiding the development of new vaccines
- Guiding the development of new therapies