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Grant: The Human Herpesvirus 6A U45 Gene Product: Role in Immune Dysfunction PI: Prof. Marshall Williams, PhD, Ohio State University, USA Several studies have demonstrated that HHV-6 disrupts normal immune function, suggesting that HHV-6 acts as an immunosuppressive agent. Specifically how HHV-6 causes immune suppression is currently unknown. A study led by Dr. Marshall Williams, Professor of Molecular Virology, Immunology, and Medical Genetics at The Ohio State University, aims to prove that the human U45 gene creates a product specific to HHV-6 which induces immune dysfunction. Dr. Williams and his team have already proven that a protein produced by a similar gene of Epstein-Barr virus causes immune dysfunction. Because HHV-6 encodes for a product similar to the Epstein-Barr virus protein, Dr. Williams believes the U45 gene product could cause immune dysfunction in HHV-6 infected patients as well. Positive findings from this study could help explain how HHV-6 suppresses the immune system in HHV-6 associated diseases. Additionally, results from this study could further development of compounds which block the production of the U45 gene product, providing therapeutic potential. To date, Prof. Williams has successfully cloned the U45 gene product. His further objectives are to purify both the recombinant U45 gene and recombinant U45 gene product and then demonstrate in vitro that U45 gene product i.e. UTPase inhibits T-cell blastogenesis in unstimulated PBMC’s and will also induce the up regulation of several inflammatory cytokines including TNF-alpha, IL-1, IL-6 and IL-10. The UTpase is expressed during lytic phase of virus replication and may also be produced during abortive infections.
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