Project 463159

Kaposi's sarcoma-associated herpesvirus (KSHV) is the infectious cause of Kaposi's sarcoma (KS), an unusual skin cancer with a bruise-like appearance which develops from the unrestricted growth of cells that line our blood vessels. Most cells in KS lesions harbor KSHV in a dormant state called latency, but a small percentage of latent cells undergo spontaneous reactivation and full replication to make new KSHV virions. These virions infect neighboring cells, allowing the KS lesion to spread and the cancer to be maintained. Unlike most tumour viruses that cause cancer in humans, KSHV only causes tumours when it replicates and infects new cells. KSHV infection of new cells is called primary infection, and it is the least understood aspect of KSHV growth. What we do know is that in a newly infected cell, KSHV attempts to replicate and copy its genome prior to settling into latency. When this step of viral genome amplification is blocked, latency fails to be established. Using a panel of viruses with mutations in a region called kaposin, our lab has revealed that the kaposin gene cluster is important for viral genome copying that occurs after primary infection. With this research, we propose to understand the role of the kaposin region in primary infection and latency establishment. This work is important because it will show us new ways that we can block KSHV primary infection and thereby block KS tumour growth and spread.