Fred L. Homa, PhD

The packaging and cleavage of replicated viral DNA into preformed capsids is a critical step during herpes simplex virus type 1 (HSV-1) infection. This process requires the products of seven viral genes: UL6, UL15, UL17, UL25, UL28, UL32, and UL33.  The UL6 protein assembles as a dodecameric complex at one of the twelve capsid vertices and functions as a portal through which viral DNA enters and exits the capsid and may be the nucleation complex for capsid formation. The UL15, UL28, and UL33 proteins comprise the viral terminase complex that functions to cleave and package the viral genome while the UL17, UL25, and UL36 proteins form part of the complex termed the capsid vertex-specific component (CVSC) that is required for both the cleavage and stable packaging of DNA-filled capsids. The UL32 protein is the least well characterized, but may play a role in localizing capsids to sites of DNA packaging. The structure of the HSV capsid portal vertex was resolved in recent cryo-electron microscopy (cryoEM) reconstructions of the virion capsid by successfully discriminating it from the other vertices. This structure revealed that the pUL6 portal dodecamer is anchored to the capsid by interactions with the peri-pentonal triplexes as well as density corresponding to a set of helices attributed to the CVSC proteins. Our research is focused on understanding the functions of the CVSC components, their interaction with the portal vertex and with the terminase complex in cleavage and retention of the packaged viral genome.