Disruption of Type I Interferon Induction by a KSHV Homologue of IPS-1

Project Abstract Herpes infections represent one of the most common viral infections that exists in the world.

These viruses can be subclinical or as in the case of Kaposi?s Sarcoma Associated Herpesvirus (KSHV) they can lead to dangerous diseases such as cancer. KSHV is well known in AIDS patients to cause Kaposi?s Sarcoma (KS) and several other lymphoproliferartive diseases.

Type I Interferon is well known to be the body?s natural anti- viral system and almost all viruses that cause infection in humans have devolved ways to block or use this system to enhance their replication in the host.

We have found a novel ORF within the genome of KSHV that seems to be a viral homologue of the IPS1 protein, a critical adaptor of the Type I Interferon induction pathway. This protein is highly expressed during KSHV lytic viral replication.

The overall goal of this application is to determine how KSHV uses this novel viral protein to manipulate the innate immune system that should normally limit KSHV replication.

In the first specific aim, we will focus on determining how KSHV uses this gene to disrupt IFN as well as replicate efficiently.

In the second aim, we plan to determine the importance of this novel gene by the construction and characterization of a KSHV deficient in this viral homologue of IPS1.

The long-term goal of this project is to determine how KSHV immune modulation occurs in the goal of blocking this manipulation and limiting KSHV replication.