Edgar Meinl

The fight of viruses against apoptosis.

The induction of apoptosis of virus-infected cells is an important host defense mechanism against invading pathogens. Some viruses express anti-apoptotic proteins that efficiently block apoptosis induced by death receptors or in response to stress signaled through mitochondria. Viral interference with host cell apoptosis leads to enhanced viral replication and may promote cancer.

Anti-apoptotic strategies of lymphotropic viruses

Induction of apoptosis of virus-infected cells is an important host cell defence mechanism. However, some viruses have incorporated genes that encode anti-apoptotic proteins or modulate the expression of cellular regulators of apoptosis. Here, Edgar Meinl and colleagues discuss recent evidence that viral interference with host cell apoptosis leads to enhanced viral replication, and to evasion of cytotoxic T-cell effects.

Human herpesvirus-8: Dysregulation of cell growth and apoptosis

Publisher Summary This chapter discusses the dysregulation of cell growth and apoptosis for human herpesvirus-8 (HHV-8). Induction of apoptosis, cell cycle arrest, and activation of cellular immunity are the typical responses of the host to viral infection. Different viruses have developed different strategies to overcome these defense mechanisms. Block of apoptosis is required to ensure efficient production of progeny before lysis of the cell occurs. Expression of human IL-6 and the IL-8 receptor are induced by Epstein-Barr virus (EBV), whereas homologs to both genes can be found in the HHV-8 genome. The function of these genes may be to stimulate proliferation of target cells, thus both increasing the pool of cells that can be infected and enhancing the conditions for viral replication in stimulated cells, are not able to replicate in resting cells. To ensure efficient replication, viruses have a vital interest to overcome the typical cell cycle arrest in G 0 /G 1 . It is ensured by k -cyclin, a cyclin-D homologue resistant to inhibition by several cyclin-dependant-kinase-inhibitors. Deregulation of the G1/S checkpoint is a common feature of many oncogenic viruses and of several malignant tumors. The HHV-8-encoded cyclin makes it obvious that antiviral and tumor-suppressing pathways converge at the same regulatory proteins. Thus, by ensuring persistent infection and efficient productive replication, viruses accidentally contribute to oncogenesis.

T cell transformation byHerpesvirus saimiri: Immortalized cells from human and rhesus monkey share essential properties

6/69 EXPRESSION OF EBNA2 INDUCES CD21/CR2 ON B AND TCELL LINES AND SHEDDING OF SOLUBLE CD21 ANTIGEN C. Larcher, B. Kempkes, E. Kremmer, W.M.Prodinger, M. Pawlita, G.W.Bornkamm and M.P.Dierich Stable transfection of a gene encoding EpsteinBarr virus nuclear antigen 2 (EBNA2) as a fusion protein with the hormone binding domain of the estrogen receptor was used to study expression of CD21 and other surface markers in different cell lines. Special emphasis was put on cell lines with a normally low expression of CD21, especially on T-cell lines. After induction of EBNA2 a substantial increase in CD21 mRNA was observed as well as increased production of membrane CD21. This was found not only in cell lines of B-cell origin but also in the T-cell line Jurkat. Moreover, the amount of CD21 was quantitated by means of a fluorescent immunoassay, and found to correlate to the presence of EBNA2 protein. A decrease in EBNA2 abundance was associated with complete loss of cell associated CD2q. As we could also detect large amounts of soluble CD21 (sCD21) in the supernatant of the transfected cell lines, which even exceed the total amount contained in the respective cell lysates, this indicates considerable shedding of the newly synthesized receptor molecules induced by EBNA2 comparable to the situation described for CD23. It further provides an explanation of our recent findings of increased sCD21 levels in sera of patients with EBV associated disease and suggests a possible additional function of EBNA2 in vdvo.