Poliovirus Receptor: From Viral Entry to Cancer Treatment
Delve into the biology of a cellular receptor, from its role in the body and its exploitation by poliovirus to its new potential in targeting cancer cells.
Poliovirus is the pathogen responsible for poliomyelitis, a disease that can lead to paralysis. For a virus to infect a person, it must first enter their cells by binding to a specific point on the cell surface, much like a key fits a lock. This initial binding begins the viral replication cycle within the host.
Identifying the Cellular Doorway for Polio
The cellular protein poliovirus uses to enter cells is the Poliovirus Receptor (PVR), also known by its scientific designation, CD155. This receptor is a glycoprotein that extends from the surface of certain human cells, acting as a docking station for the virus. The presence of CD155 determines which cells the poliovirus can infect.
The CD155 protein is found on various cell types, including cells in the gut, certain immune cells, and motor neurons in the central nervous system. The virus’s ability to infect these motor neurons leads to the paralytic symptoms of poliomyelitis.
Structurally, CD155 is a transmembrane protein with parts inside, outside, and passing through the cell membrane. Its external portion has three folded sections called immunoglobulin-like domains. The poliovirus specifically attaches to the outermost domain, D1, to initiate infection.
The Viral Invasion Mechanism
The invasion begins when a poliovirus particle encounters a cell with the CD155 receptor. The virus’s protein shell, or capsid, has a recessed area on its surface described as a “canyon.” The CD155 receptor fits into this canyon, establishing a firm connection between the virus and the cell.
Once attached, the interaction with the CD155 receptor triggers a significant, irreversible change in the virus’s structure. At physiological temperatures, the viral capsid expands and becomes less stable. This structural alteration prepares the virus for the next stage of entry.
This destabilization allows the altered capsid to form a pore in the host cell’s membrane. Through this channel, the virus injects its genetic material, a single strand of RNA, into the cell’s cytoplasm. The host cell’s machinery then uses this viral RNA to produce new virus particles.
The Receptor’s Everyday Biological Job
The CD155 receptor exists for the body’s own functions, not for the poliovirus, which has evolved to exploit it. In the human body, one of its primary roles is in cell adhesion. It helps cells stick to one another and to the surrounding extracellular matrix, the network of molecules providing structural support to tissues.
CD155 is also involved in the immune system. It is present on immune cells and interacts with proteins on other immune cells, like T cells and natural killer (NK) cells. These interactions can either activate or inhibit immune responses, helping to regulate the body’s defenses. For example, CD155 can bind to a receptor called DNAM-1 to promote the killing of tumor cells by NK cells.
This receptor is part of the nectin-like family of proteins, which are involved in organizing junctions between cells. Its presence on nerve and epithelial cells points to its role in tissue organization and signaling.
Repurposing the Receptor for Cancer Therapy
The receptor that makes cells vulnerable to poliovirus is now being explored as a target for cancer treatment. This approach, oncolytic virotherapy, uses genetically modified viruses to destroy cancer cells. Scientists have engineered a version of the poliovirus that cannot cause poliomyelitis but retains its ability to bind to the CD155 receptor.
This strategy is effective because many types of cancer cells express high levels of CD155 on their surfaces. For example, aggressive brain tumors like glioblastoma have an abundance of CD155, while it is expressed at low levels in normal brain tissue. This difference allows the modified virus to selectively target cancer cells, leaving healthy cells unharmed.
The engineered virus, sometimes called PVS-RIPO, is a chimaera of the poliovirus and a human rhinovirus. After being introduced, the modified virus binds to CD155 receptors on tumor cells and infects them. Once inside, the virus replicates, causing the cancer cell to burst and release new virus particles that infect neighboring cancer cells.
This process of cell destruction also alerts the immune system. The death of cancer cells releases tumor antigens, which can trigger a targeted immune response against the remaining tumor. The modified poliovirus therefore kills cancer cells directly and stimulates the patient’s immune system to attack the cancer.