The Epstein Barr virus (EBV) is widespread since more than 90 percent of the world's population is infected, with very different consequences. Although the infection usually does not affect people, in some it can cause glandular fever or various types of cancer. Researchers of German Cancer Research Center (DKFZ) have now discovered why different strains of viruses cause very divergent disease courses, as published in Nature Microbiology
Glandular fever (infectious mononucleosis) occurs mainly in Europe and North America and usually affects teenagers or young adults. In equatorial Africa, Burkitt lymphoma is associated with EBV infection. And in Taiwan, southern China and Southeast Asia, the virus often causes nasopharyngeal carcinomas. This is one of the most common types of cancer in young adults in these countries.
“Sometimes nasopharyngeal carcinomas are also seen here, but really rarely,” says DKFZ researcher Henri-Jacques Delecluse. “A possible explanation for these differences that are responsible for different types of viruses. And now we have found evidence of that, ”explains Delecluse.
In the laboratory, Delecluse and his team studied a virus strain that had previously been isolated from a nasopharyngeal carcinoma. M81, as this particular type of virus is called, has certain peculiarities.
Therefore, the researchers had already discovered that M81 infects not only the B cells of the immune system, but also the epithelial cells of the nasal mucosa membrane very efficiently. By contrast, virus strains that cause mononucleosis in Europe almost only infect B cells. And although the virus strains that are common here cause infected B cells to multiply in a Petri dish, they do not produce new virus particles. , unlike M81.
As the DKFZ researchers discovered, one of the reasons for this different behavior is a genetic element called EBER2, of which there are many different variations. EBER2 is what is called a ‘non-coding RNA’ (ncRNA), in other words, an RNA fragment that does not contain a model for protein molecules. M81 has an EBER2 variant that is particularly often found in EBV strains of nasopharyngeal carcinomas.
To discover how this variant affects the behavior of the virus, DKFZ researchers used molecular biology tools to extract EBER2 from the M81 genome. “The virus could no longer multiply in infected cells,” Delecluse said. Even when an EBER2 element of a virus strain that is widespread in Europe was inserted into the M81 virus, it could no longer produce virus particles.
The researchers also discovered how EBER2 helps M81 multiply. “EBER2 of M81 stimulates the production of CXCL8, a cytokine that plays an important role in inflammation and carcinogenesis,” Delecluse explained.
“The EBER2 RNA is in small envelopes in the infected cell and transported to neighboring cells, they also begin to produce CXCL8,” he continues, explaining that this eventually stimulated the virus to produce offspring.
“Therefore, we have finally found evidence that different types of viruses may be responsible for different variants, Delecluse notes. This finding is a strong argument for continuing vaccine research to develop protection against the most dangerous strains of EBV in the future. ” The human papillomavirus (HPV) vaccine, which can cause cervical cancer, already uses a similar principle.