Many viruses are covered in proteins that extend from their surface, giving them a crown-like or spiky appearance. These structures, known as spike proteins, are glycoproteins, meaning they are made of both proteins and carbohydrates. They are a common feature of enveloped viruses, which have an outer protective membrane. These proteins are functional tools that allow a virus to penetrate host cells and begin an infection.
The Role of Spike Proteins in Viral Infection
A virus enters a host cell using a “lock-and-key” model, where the spike protein is the key and a specific molecule on the host cell, called a receptor, is the lock. For a virus to successfully infect a cell, its spike protein must have the correct shape and chemical properties to fit into the host cell’s receptor. This specificity determines which types of cells a virus can infect.
An example of this interaction is seen with SARS-CoV-2, the virus that causes COVID-19. The spike protein on SARS-CoV-2 is designed to bind to a receptor on human cells known as angiotensin-converting enzyme 2 (ACE2). The spike protein has different parts, including a region called the receptor-binding domain (RBD), which is the precise part of the “key” that fits into the ACE2 “lock.” This binding is the first step in the infection process.
Once the spike protein has attached to the ACE2 receptor, it triggers changes in its own structure. These rearrangements are assisted by host enzymes, like TMPRSS2, which cleave the spike protein at specific sites. This cleavage activates the protein, causing it to unfold and expose a segment that facilitates the fusion of the viral envelope with the host cell’s membrane. This fusion creates an opening for the virus’s genetic material to enter the cell, where it hijacks the cell’s machinery to replicate.
The Immune System’s Response to Spike Proteins
When a virus infects the body, the immune system identifies specific foreign components known as antigens, and the spike protein is a primary one. Because spike proteins are located on the outer surface of the virus, they are highly visible to immune cells. The immune system recognizes these proteins as invaders, triggering a defensive response.
A major part of this defense involves the production of antibodies. B cells, a type of immune cell, create antibodies that are precisely shaped to match and bind to the spike protein. Some of these are neutralizing antibodies, which are particularly effective. Neutralizing antibodies attach to the spike protein in a way that physically blocks it from binding to host cell receptors, disarming the virus and preventing it from infecting new cells.
The immune system also establishes long-term defense by creating memory B cells and T cells that retain the “memory” of the spike protein’s shape. T-follicular helper cells assist B cells in producing high-quality antibodies. This immune memory allows the body to mount a much faster and more powerful antibody response if it encounters the same viral spike protein in the future.
Targeting Spike Proteins for Medical Intervention
The spike protein’s function in viral entry makes it an ideal target for medical technologies designed to prevent or treat viral diseases. The primary strategy is to train the immune system to recognize the spike protein ahead of time without exposing the body to the actual virus. This is the principle behind many modern vaccines.
Messenger RNA (mRNA) vaccines, such as those developed for COVID-19, exemplify this approach. These vaccines do not contain any part of the virus. Instead, they deliver a small piece of genetic code, the mRNA, which provides instructions for the body’s own cells to manufacture a harmless version of the spike protein. Once cells produce the spike protein, the immune system recognizes it as foreign and mounts a response, creating protective antibodies and memory cells.
Other medical interventions also target the spike protein.
- Viral vector vaccines use a harmless, modified virus to deliver the genetic instructions for making the spike protein.
- Protein subunit vaccines include harmless pieces of the actual spike protein itself, which the immune system can then learn to recognize.
- Therapeutic treatments like monoclonal antibodies use lab-engineered antibodies that mimic the body’s natural neutralizing antibodies, binding directly to the spike protein of an invading virus to block it from entering cells.
Spike Protein Variation and Viral Evolution
RNA viruses are prone to making mistakes during replication, resulting in genetic mutations. When these mutations occur in the gene that provides instructions for the spike protein, it can lead to alterations in the protein’s structure. This process of mutation and selection is a natural part of viral evolution.
A new version of a virus that has accumulated several mutations is known as a variant. While some changes to the spike protein may be insignificant, others can alter the virus’s behavior. For instance, a mutation might change the shape of the receptor-binding domain, making it attach more tightly to host cell receptors. This can lead to a variant that is more transmissible than its predecessors.
Other mutations might alter the surface of the spike protein in ways that make it harder for the immune system’s antibodies to recognize and bind to it. This is known as immune evasion, and it can reduce the effectiveness of immunity gained from a previous infection or vaccination. The emergence of variants with altered spike proteins, such as Delta and Omicron, explains why updated vaccines are sometimes needed.