Projects in Our Lab: Herpesvirus Replication
Jessica Lawler: During HCMV infection, replication of the viral genome, transcription of viral genes, and encapsidation of the viral genome is thought to happen in or at the periphery of large, non-membrane-bound structures in the nucleus of the infected cell known as viral replication compartments. A large number of host and viral proteins, including nucleolin (NCL), a host protein involved in nucleolar maturation; UL44, the viral processivity factor; and UL84, a viral replication factor of unknown function, localize to these compartments. These specific proteins seem to colocalize at the periphery of replication compartments, where viral DNA synthesis is believed to occur. Additionally, these proteins have been shown to associate when immunoprecipitated during infection. Viral replication compartments share similarities with RNP granules which have been shown to form liquid droplet structures in vitro and in vivo, and NCL, UL44, and UL84 all contain low complexity sequences and nucleic acid binding domains that tend to be enriched in proteins that make up liquid droplet structures. These data support a model that NCL, UL44, and UL84 form interactions that at least partially mediate the formation of replication compartments into liquid droplet-like structures, where viral and host proteins necessary for viral replication are compartmentalized. Jessica's research focuses on validating the interactions between these three proteins in vitro and identifying the interactions with form and maintain HCMV replication compartments in the host nucleus.
Purba Mukherjee: Visualization of the interaction between the Herpes simplex virus 1 polymerase (UL30) and its processivity factor (UL42) using biochemical, x-ray crystallographic, and/or EM techniques.
Collaborator: Coen Lab