Genetics & Cell Biology
Viral epidemiology
Generally, the potential impact of a virus on a population is defined by two factors: virulence and transmissibility. Virulence refers to the overall severity of the disease caused by the virus and its associated symptoms. In the context of the COVID-19 pandemic, virulence can be assessed by looking at a variety of factors such as total mortality caused by the virus, the overall long term costs of infection (e.g. long-COVID and tissue damage), and the costs associated with decreased access to health care due to overwhelmed hospital systems.
Transmissibility is defined by the various factors associated with the virus’ ability to infect new hosts via contagious individuals. This can be quantified by estimating the basic reproductive number (R0) of the virus, which is defined by the average number of individuals an infected individual will spread the virus to.
SARS-CoV-2 anatomy
The external physical appearance of SARS-CoV-2 is characterized by the numerous spike proteins protruding from the viral membrane. These spike proteins play a crucial role in the virus’ reproductive success. They allow the virus to attach to the surface of potential host cells, and aid in viral entry. These spike proteins also happen to be the primary target of hosts’ immune systems. Envelope proteins embedded in the viral membrane aid in the assembly of new viruses after replication is complete. The viral membrane provides these envelope proteins with a surface to anchor to, and also protects the internal components of the virus.
The internal components of the virus are the components that ultimately make it into the host cell and aid in the process of viral replication. The genetic material of the virus contains instructions to produce the proteins required to make more viruses. The nucleoproteins are bundled with the RNA and aid in guiding it towards RNA polymerase, so replication can occur.
SARS-CoV-2 life cycle
The SARS-CoV-2 virus goes through a series of steps in order to replicate within host cells.
Step 1 – Viral attachment: Spike proteins on the surface of the virus bind to a transmembrane protein on the surface of the host’s cell (called the ACE2 protein).
Step 2 – Membrane fusion: A transmembrane enzyme on the surface of the host’s cell called TMRPSS2 interacts with the spike proteins. This allows the spike proteins to initiate the process of membrane fusion by penetrating the membrane of the host. Once the membrane is penetrated, the viral membrane and cell membrane fuse together, allowing the contents of the virus to enter the cell.
Step 3 – Viral replication: Once inside the cell, the viral genetic material is replicated. Some of this genetic material is turned into viral protein and some is used as the genome for the next generation of viruses. Once the new proteins and new genetic material is synthesized, new virus particles are assembled in the cell.
Step 4 – Viral shedding: Once new viruses have been assembled, they exit the cell via exocytosis. This involves being packaged into vesicles by the host’s Golgi bodies, and being exported to the surface of the cell, where they can leave and infect more cells.
SARS-CoV-2 genome
Viral genomes are made up of a long chain of nucleic acids, supported by a sugar-phosphate backbone. Some viruses have a genome that is made entirely of DNA, while others have RNA genomes. Some viruses have a single-stranded genome, others have a double-stranded genome.
SARS-CoV-2, the virus that causes COVID-19, is a single-stranded RNA virus. Single stranded RNA viruses are responsible for a variety of human diseases including MERS, SARS, West Nile, dengue fever, hepatitis, and the common cold.
Most viruses have relatively small genomes compared to living organisms. The SARS-CoV-2 genome, for example, contains only 11 genes and is made up of 29,903 base pairs. Comparatively, a typical bacteria genome contains roughly 5 million base pairs coding for 5,000 proteins, and the human genome contains around 3 billion base pairs.
Spike protein and natural selection
Spike proteins are located on the outside of a virus and are specialized to bind to protein receptors on prospective host cells. The SARS-CoV-2 spike protein binds to “ACE2”, a receptor that is abundant on our respiratory system cells. Any mutations on the gene coding for the spike protein will result in changes to the chain of amino acids comprising the spike protein. These changes influence the ability of the virus to attach and subsequently infect human cells.
Mutation rates are much higher in viruses than in living organisms, and viruses replicate very quickly. Since mutations are random, most do not improve the ability of the virus to infect and replicate and therefore do not persist in the population. However, a small proportion of these mutations can be beneficial. These mutations may help virus particles to more effectively gain entry to host cells, help them replicate in shorter periods of time, or even help virus particles avoid immune system countermeasures, replicating more efficiently, or evading immune responses to infection. Viruses with these advantageous mutations will pass the new traits to the next generation during replication.
