Herpesviruses are some of the most complex and interesting viruses infecting humans. These viruses are capable of establishing lifelong dormant infections - many of us are infected with at least one type of herpesvirus, and do not even know it. Unfortunately, these viruses can have detrimental effects on the immunocompromised, yet there is no universal vaccine or cure.
We are focused on Herpes Simplex Virus Type 1 (HSV-1), a neuroinvasive virus infecting 70% of the human population. Currently, we combine a variety of biophysical tools, along with chemistry and virology, to understand how capsid-centric processes contribute to viral replication. The goal of our work is to provide new insights into how we can more effectively combat this virus.
All herpesviruses require the assembly of a capsid shell to protect the viral genome. This process is essential for successful viral replication and is an attractive therapeutic target. We aim to develop novel biophysical methodologies to dissect the HSV-1 capsid assembly pathway, informing the design of assembly inhibitors and provide new tools for other virologists.
Herpesviral capsids overcome amazing biological feats, capable of housing a viral genome under extreme amounts of pressure, while trafficking through the cellular milieu. Despite these forces, the capsid shell stays intact. We seek to understand how they achieve such feats and also understand the limits of these properties.
CAPSID NUCLEAR ESCAPE
The nucleus is the site of herpesviral replication, including capsid assembly and packaging. Here, capsids face yet another obstacle - escaping the nucleus to become mature virions in the cytoplasm. The large size of herpesviral capsids precludes nuclear pore transport and instead, capsids bud out of the nucleus, in a process termed nuclear egress. Budding is mediated by the viral nuclear egress complex (NEC), a virally-encoded budding machine, essential for viral replication. We are currently designing various inhibitors to block NEC activity, both as therapeutic and functional tools.