Contributed by Guest Blogger: E. Raganit ’14
Epstein-Barr virus (EBV), also known as Human Herpes virus 4, greatly influences the development of many cancers. Latent membrane protein 1 (LMP1) was found to be an important oncogene of EBV in that it has transforming properties. Exosomes, vesicles that are secreted to aid in the transfer of proteins, mRNAs, and microRNAs to neighbor cells, have just recently been discovered as a mechanism that may be manipulated by both cancer cells and virus-infected cells. They are found in many biological fluids, including blood and urine. It was also recently concluded that viruses may use the exosome pathway to evade the immune system.
In a study done by the Lineberger Comprehensive Cancer Center and the Department of Microbiology-Immunology of the University of North Carolina, the group of scientists wished to test the effects of LMP1 on the exosome composition. The group harvested cells from the nasopharyngeal cell (NPC) C666 cell line that retained EBV, but also had low levels of LMP1 and compared it to both a C666 line that strongly expressed LMP1 exosomes (C666-LMP1) and a C666 control (C666-pBabe). Both the C666 and the C666-LMP1 exsosomes contained epidermal growth factor receptors.
In a test to determine if LMP1 had the ability to activate signaling pathways, the scientists exposed human umbilical vein endothelial cells (HUVECs) to exosomes. Results showed that the C666-pBabe exosomes were capable of activating the signaling pathways, but the C666-LMP1 exosomes induced activation in higher levels. This led to the conclusion that LMP1 increased the release of the epidermal growth factor receptor into exosomes, causing the activation of the ERK pathways. Findings also showed that EBV virus used the exosomal system in order to secrete molecules and viral-encoded proteins.
With the knowledge that through these exosome pathways, viruses may escape the immune system with the LMP1 activating biological channels, is it possible to create some sort of drug that halts all LMP1 processes in the hopes that the Epstein-Barr virus will not be able to continue transforming cells into tumor cells? Is it possible for the immune system to enter the exosome pathways in order to stop the EBV from further spreading?
Good post Estello. The possible use of exosomes in viral evasion of the imumune response was surprising in many ways, most notably in the fact that this capability of viruses has not been recognized for so long. It is a remarkable commentary on viruses that even in our so called golden age of biology we still cannot even pretend to understand the myriad ways that viruses can exploit cellular machinery. Even more surprising is that this discovery was made using Epstein-Barr Virus, a relatively well explored pathogen. Though this was only an exploratory study, I would be interested to know how this and other inquiries into other ways viruses can exploit cells affect searches for cures, or even if scientists discover similar, notable characteristics of known illnesses of great virulence.