Defeating Infectious Agents — 9

More than sixty years ago, the Epstein-Barr virus was the first demonstration of a cause and effect for a virus to induce cancer, specifically Burkitt’s lymphoma. By electron microscopy, the virus could be seen replicating in the tumor cells. But 95 percent of the world’s population has a lifelong infection from this virus without symptoms, the most common persistent viral infection in humans. Epstein-Barr preferentially infects B cells, and, in culture, the virus induces unbridled B cell proliferation, a reflection of its malignant potential. But an additional factor beyond the Epstein-Barr virus infection appears to be required for development of lymphoma (a chromosome rearrangement) and nasopharyngeal carcinoma (an epigenetic event). Less is known about what factor accounts for this virus’s link to stomach cancer. Given that, globally, Epstein-Barr virus is involved in 1.5 percent of cancers, we may be waiting some time for sufficient research to produce a vaccine.

For many years there was a potential link between Epstein-Barr and multiple sclerosis (MS). MS, an autoimmune disease affecting nearly two million people, is more frequent among people who have infectious mononucleosis, often caused by Epstein-Barr. Some pathology tissue postmortem samples from people who had MS contained Epstein-Barr virus. And tellingly, individuals with MS have been seen to have increased levels of antigens directed against Epstein-Barr virus. In 2022, a major report from over ten million young adults in the US military advanced the case for a causal relationship between the two maladies.

From sixty-two million blood samples obtained over a twenty-year period (1993–2013), the timing of Epstein-Barr infection could be determined, correlated with the diagnosis of MS that occurred in 955 individuals, and compared with controls who did not develop MS. The risk of MS increased thirty-two-fold after Epstein-Barr infection, was not associated with any other viruses, and a biomarker for nerve cell injury (serum neurofilament light chain) increased after the Epstein-Barr infection. The conclusion was that this common virus was “the leading cause of MS.”

Subsequent reports cemented the case. In the cerebrospinal fluid from patients with MS, antibodies to Epstein-Barr nuclear antigens were found. Molecular mimicry has been a leading proposed mechanism, supported by the finding that a Glial CAM protein in nerve tissue or alpha-crystallin B, expressed by oligodendrocytes, looks like an Epstein-Barr nuclear antigen to the body’s immune system. So, the person’s immune response to Epstein-Barr infection is to direct antibodies to it, but these antibodies attack neurons too, because of the look-alike proteins. This lays the foundation for a self-perpetuating autoimmunity loop. In the early phase at initial diagnosis of MS, T cells directed to the Epstein-Barr-infected B cells are found in the cerebrospinal fluid.