Session 1E: The Portal Protein in Herpes Simplex Virus 1

Herpes viruses, including herpes symplex virus type 1 (HSV-1), are human pathogens of a significant disease burden within the population. They are large, double-stranded DNA viruses with virions comprised of four layers: envelope, tegument, capsid, and viral DNA. The herpesvirus capsid dynamically interacts with viral and cellular proteins during multiple steps of the infectious cycle. The capsid selfassembles from six viral proteins with one unique vertex comprised of the portal protein encoded by the gene UL6. It is thought that viral DNA is packaged and released through this portal. A current obstacle exists in considering the study of this viral protein-- scientific studies have yet to achieve a successful incorporation of a functional tag within viral pUL6. Therefore, this project aims to determine the possibility of introducing a peptide tag within pUL6, which would allow for a more focused analysis of the viral protein during infection. We propose to introduce a small amino acid motif within UL6 that upon substrate addition can catalyze a chemical reaction yielding a fluorescent signal, which can be monitored in vitro. Through the incorporation of this catalytic motif, it is possible to exploit methods such as click chemistry and high-resolution fluorescent microscopy to shed light on pUL6 function during infection. Toward this aim, this project investigates regions of pUl6 which might tolerate modifications. Based on the current literature and advances made possible through this study, putative sites for incorporation of a tag within the sequence of pUL6 have been identified and will further be examined in the context of infection.