Research Description:

Cellular Proteins that Associate with KSSM

Kaposi’s sarcoma-associated herpesvirus (KSHV) has been directly linked to human malignancies such as lymphoma and Kaposi’s sarcoma. It is believed that the virus maintains a persistent infection in B lymphocytes of the infected host but will remain latent until it is reactivated. Once KSHV enters the lytic phase, it replicates its genome and ultimately lyses the host cell, releasing viral progeny. During the lytic phase, the virus also synthesizes several protein products, which modulate cellular functions and may contribute to the development of cancer.

An example of such a protein in KSHV is called KS-SM, which is named after the homologous Epstein-Barr virus protein, SM. SM is involved in several aspects of gene regulation, such as nuclear mRNA stabilization, post-transcriptional processing and nuclear RNA export. KS-SM much like SM is also responsible for mRNA stabilization and is thought to shuttle from the nucleus to the cytoplasm. My mentor’s research laboratory has shown that EBV also takes advantage of protein products made by the host cell and uses them to facilitate the survival and growth of the virus. SM recruits these cell proteins, binds to them, and utilizes them to specifically increase viral gene expression as well as affect cellular processes. It is the goal of my research project to find such proteins that interact with our protein of interest, KS-SM.

It is very interesting to see how viruses have evolved to take full advantage of their environment. They take advantage of the cell’s gene products and use it against them to further their own ends. Investigating such interactions is important in order to find appropriate drug therapy to treat viral infection. By knowing which host cell proteins interact with proteins made by the virus one could potentially target these interactions. In the case of KS-SM, one can envision such interactions leading to destabilization of viral mRNA and inhibition of viral replication. In addition, we hope to understand the nature of interactions between KS-SM and cell proteins. By better understanding the mechanism of mRNA stabilization, one could to use these findings and apply them to therapy.