Of all the viral infections that affect humans, Epstein-Barr virus (EBV) is one of the most common. Upon initial infection, the virus causes mononucleosis in some children and young adults; this disease is characterized by non-specific symptoms, such as fever, as well as exhaustion which in some cases can last for several months. Until now, it was not clear why a first EBV infection leads to mononucleosis in only a minority of people, while most have no symptoms. EBV proliferation in humans is normally fought off by T cells as part of an antiviral immune response. Through this important mechanism, certain EBV components (peptides) are presented to T cells by a specific molecule (HLA-E), which is found on the surface of cells infected with the virus.
This triggers a non-classical T cell response that leads to the destruction of infected cells. Due to a genetic variation (HLA-E*0103/0103), approximately one third of the population naturally has more HLA-E molecules on EBV infected cells. Medicine has not yet been able to explain why the Epstein-Barr virus triggers infectious mononucleosis in some people with initial infections and not in others. Now, a new investigation at MedUni Vienna’s Center for Virology has shown that the risk of developing mononucleosis after the first EBV infection strongly depends on this specific immune response and could be a potential target for vaccine development. Not only have researchers identified the EBV-specific immune response as the cause of this phenomenon, but the response could also be a potential target for research into preventive measures.
First author of the study, Hannes Vietzen, explained: ‘Our research has revealed that people with the genetic variation HLA-E*0103/0103 have a lower risk of developing infectious mononucleosis than those who do not have the variation. Our laboratory experiments demonstrated that this gene variation is associated with a highly pronounced EBV-specific nonclassical immune response. This immune response was still measurable years after the initial EBV infection; and generally provides long-lasting protection against re-infection from the Epstein-Barr virus.So it might be worth to focus our attention on this mechanism in view of the development of new vaccines in the future.Therefore, the analysis of EBV strains found in these patients could be useful to identify patients with high risk at an early stage and treat them in good time”.
Another study result could also open up new diagnostic options: The combination of the unfavorable HLA-E genetic variation with certain EBV peptides also appears to play an important role in the development of EBV-associated lymphomas in transplant recipients. The findings were recently published in the American Society of Hematology journal Blood.
- Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
Vietzen H, Furlano PL et al. Blood 2022 Dec 7; 2022017650.
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