In people with severely damaged immune systems, JC can cause an untreatable, usually fatal brain disease. Now, an international research team examining the viral capsid has identified binding sites for neutralizing antibodies. these sites could be used to stop JC polyomavirus infection. Led by Professor Thilo Stehle of the Interfaculty Institute of Biochemistry at the University of Tübingen, the study also involved researchers from Brown University in the United States and Universitätsspital Zürich. These new insights into the interactions between JC polyomaviruses and the human immune system lay the foundation for the development of treatments and vaccines. The study has been published in the journal PNAS.
JC-Polyoma virus (JCPyV) is widespread. “It only becomes dangerous when the body’s immune system is severely weakened, for example in people with advanced HIV, patients taking strong immunosuppressants or people who have undergone organ transplants or have certain types of cancer,” explains Thilo Stehle. In these cases, the virus can enter the central nervous system through the bloodstream and cause a disease called progressive multifocal leukoencephalopathy (PML). This disease destroys the brain and is incurable, and therefore usually fatal.
Neutralizing antibodies
For the study, the research team relied on the observation that some patients survive PML.
Their bodies manage to neutralize the attacking JC polioviruses so that they can no longer enter the body’s cells. the infection has stopped.”
Professor Thilo Stehle, Interfaculty Institute of Biochemistry, University of Tübingen
The immune system achieves this neutralization by producing precisely tailored antibodies. These antibodies attach like a lock to binding sites on the viral envelope. “This prevents the binding site from being available for binding to another cell in the body,” explains the researcher. At the Universitätsspital Zürich, such specific antibodies against the JC envelope of polyomaviruses were isolated from patients with PML and tested for their binding properties at Brown University in the USA.
However, even when the human body fights back against JC polyomaviruses, the virus develops strategies to evade the immune system. “Genetic mutations occur in the binding sites that human antibodies use to defend against the virus. This can render the antibodies ineffective.” says Stehle, “and we looked at it in detail.” Knowledge of the structure and mechanisms of action between JC polyomaviruses and the human immune system enables the development of antibodies that can be used therapeutically against the infection, as well as vaccines.
“At the same time, there is potential for cross-protection against BK polyomavirus, which is related to JC virus and can also cause severe disease in immunocompromised individuals,” adds Stehle. “A potential vaccine could protect high-risk patients from infection with both polioviruses. Therapeutically-used small molecules that target the antibody-binding site could potentially be effective against both viruses.”
