Human herpesviruses and chronic lymphocytic leukemia

Chronic lymphocytic leukaemia (CLL) is a common and non-curable haematological malignancy. The factors leading to this malignancy still have to be elucidated but an increasing body of evidence suggests that CLL evolves from repetitive activation of particular B-cell clones through the B-cell receptor (BCR) by latent viruses or commensal bacteria. Herpesvirus infections exhibit characteristics that are highly compatible with theoretical prerequisites of an antigen-driven evolution of CLL. Herpesviruses establish latent infection with periodical reactivation and exposure of antigen to the host`s immune system, persist within the host for life-time, survive in antigen-presenting cells, are common pathogens with worldwide distribution, exhibit multiple immunomodulatory mechanisms to insure survival within the host, and may stimulate a strong humoral immune response to infection. We will address in proposed interdisciplinary study the influence of herpesvirus infections on the evolution of CLL involving specialists from the fields of virology, immunology, and haematology. The aim of the study is to substantiate a potential link between the infectious and haematological disease by screening for herpesvirus- specific binding activity of recombinant BCR derived from CLL-patients. Herpesvirus infections may be modified by available antiviral drugs or prevented by active immunization using virus-specific vaccines. Ultimately, CLL may be transformed from a non-curable to a preventable disease.