Latent infection membrane protein 1 (LMP1) is expressed in most malignances associated with EBV infection, has oncogene-like effects on immortalized fibroblasts, and is essential for EBV to efficiently transform the growth of resting primary B-lymphocytes into long-term autonomously proliferating lymphoblastoid cell lines.

Recombinant virus, genetic, and biochemical analyses have revealed that LMP1 is a constitutively active membrane receptor that appropriates signaling adapters of the tumor necrosis factor receptor superfamily to alter cell gene expression through NF κB, mitogen-activated protein kinases, or interferon regulatory factors. LMP1 signaling mediated alterations in gene expression are critical for long-term cell proliferation and survival, and this is consistent with a significant role in the development of malignancies in vivo.

Thus, there is considerable effort in clarifying the molecular mechanisms of LMP1 signaling and their effects on cell growth, survival and gene expression as a critical step in identifying targets for interventions to specifically prevent or treat EBV-related cancers, particularly in the context of immune suppression.

from Epstein-Barr Virus: Latency and Transformation

Further reading:

• Epstein-Barr Virus
• RNA Interference and Viruses
• Virology publications

Labels: EBV-related cancers, LMP1, Oncogene, Tumor necrosis factor receptor superfamily

Retroviruses cause cancer in natural or laboratory settings by a variety of mechanisms. The acutely transforming or transducing retroviruses induce tumours in animals within days to weeks. They harbour a host-cell derived gene, an oncogene, which infiltrate signalling cascades that regulate cell growth and survival.

The oncoprotein encoded by the viral oncogene is activated to dominant signalling, either by deregulated expression or as a result of a modified protein structure that uncouples downstream signalling from upstream physiological signals. The cis-acting or non-acutely transforming viruses cause disease with latency periods of months. These viruses work as insertional mutagens to promote multi-step oncogenesis, and large-scale mapping of proviral insertions in tumour DNAs provides a rich source of candidate genes with a potential role in cancer of non-retroviral aetiology.

Viral proteins may also stimulate target cells to proliferate. One example is the mouse mammary tumour virus which stimulates lymphocytes via a virus-encoded superantigen. Other examples are the mitogenic stimulation of erythrocyte precursor cells by the defective envelope protein of the mouse spleen focus-forming virus, and the direct oncogenic affect of the envelope protein of the Jaagsiekte sheep retrovirus.

Further reading: Retroviruses: Molecular Biology, Genomics and Pathogenesis

Labels: Jaagsiekte sheep retrovirus, Oncogene, Oncogenesis, Oncoprotein, Oncoviral, Oncovirus, Proviral insertions, Transforming viruses