Epstein-Barr virus

Natural infections are involved in the pathogenesis of 15-20% of all cancer in humans. In particular persistent viral infections and some bacterial infections are linked to cancer risks: hepatitis B virus, human hepatit C virus, human T-cell lymphoma virus, papilloma virus, Epstein-Barr virus (EBV), HHV-8 and H.pylori. Understanding the biology of the interaction between the host and the invading microorganism is crucial for future design of epidemiologic surveys, for identification of risk-groups, prevention, diagnosis and treatment. On the other hand natural infections as a cause of cancer opens unique possibilities to reduce the human cancer burden, by using several of these measures. Characteristic of all the cancer-associated infections known until now is that they may cause chronic or latent persistence of the virus, or bacteria in or at cells of the target tissues. This is either the result of natural strategy or of biological accidents. The subsequent cancer risk depends on direct effects of microbial genes on cellular controls systems, and/or on tissue damage and inflammatory type of responses.

All tumor-associated viruses have evolved strategies for survival and spread as part of their physiologic infection, which affects cell cycle and apoptosis control. By inducing transient proliferation in their target organ/cells they prepare for lytic replication by engaging more cells, as an amplification mechanism. Virus infections per se induce apoptosis, which may be regarded as a defence mechanism by the host/host cell. Progression from cells at risk to overt tumor only takes place if late replicative events are truncated or blocked (e.g. by integration, accidental infection of wrong cell type), if the infection cannot be handled by the immune system and/or if the infection raises an inappropriate host reaction.

Epstein-Barr virus (EBV) infection in man, illustrates these points, due to extenisve though incomplete knowledge on several of these issues. EBV is the most common virus in the human population (>90% of adults carry the virus), it normally gives rise to an inconspicuous or benign infection, paradoxically, however, under rare circumstances it induces tumors and in vitro it is very efficient in transforming its natural host cell, the B-lymphocyte.

We are studying the following aspects during the granted 1,5 yrs:

1. Activation of the physiologic program for B-cell activation and proliferation: latency in vivo

2. Subversion of apopotosis, signal transduction and transcriptional regulation: control of latency

3. Control of EBV infected B cells by helper T cells?

4. Immune escape and latency in patients at risk

5. New methods for rapid identification of genome similarities and differences

This group consists of Ingemar Ernberg, professor; Jie-Zhi Zou, graduate student; Anna Berg; graduate student; Jenny Almqvist, graduate student; Anna Friis, graduate student; �sa Gustavsson, graduate student; Katarina Gyllensten, graduate student; Fu Chen, graduate student; Anna Aleman, technician; Anita Westman, technician

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