Our Science – Buck Website
Christopher B. Buck, Ph.D.
Although work in the Tumor Virus Molecular Biology Section (TVMBS) has its roots in the molecular biology of human papillomaviruses (HPVs), the lab is now primarily focused on a different family of cancer-causing viruses called the Polyomaviridae. A great majority of healthy adults chronically shed human polyomavirus virions from the surface of their skin. At least one of these skin-dwelling polyomavirus species, Merkel cell polyomavirus, appears to cause a rare but highly lethal form of skin cancer called Merkel cell carcinoma.
The organizing focus of work in the lab is the molecular biology of the virion. HPVs and polyomaviruses have structurally similar non-enveloped icosahedral capsids that are assembled from a single viral protein (L1 for papillomaviruses, VP1 for polyomaviruses). The virions of non-enveloped viruses are dynamic structures that must undergo a range of conformational changes during different stages of the virus life cycle. Virions must be flexible enough to allow encapsidation of the viral genome, yet stable enough to withstand environmental insults encountered during transmission between hosts. Virions must also become pliable enough to release the viral genome upon infection of a host cell. Because each of these steps involves interactions with host cells, the virion must maintain a variety of evolutionarily conserved motifs capable of binding relatively invariant cellular targets. It is a general principle of virology that conserved ''Achilles heel'' motifs in the virion are structurally obscured to prevent recognition by the immune system. Understanding the nature of these conserved sites of virion vulnerability may allow the development of vaccines capable of eliciting cross-neutralizing antibody responses capable of protecting vaccinees from the full range of cancer-causing HPVs or, potentially, disease-causing polyomaviruses.
Our group has pioneered the development of HPV-based and, more recently, polyomavirus-based gene transfer vectors. These vectors (also known as pseudoviruses) are thought to deliver encapsidated reporter plasmids to the cell nucleus via pathways that resemble the infectious entry of authentic virions. In addition to their utility for studying the mechanics of infectious entry in vitro and in vivo, the reporter vectors have a variety of other applications. For example, recent collaborative projects suggest that HPV vectors may serve as vehicles for genetic vaccines targeting other viral pathogens, such as HIV. The lab has also used reporter vectors to perform analyses of polyomavirus-neutralizing antibody responses among humans. It is conceivable that such serological analyses may help uncover new links between polyomaviruses and human diseases, including cancer.
Although the core goals of the work in the lab primarily target basic science questions, it is hoped that improved understanding of the molecular biology of tumor viruses will, in the longer run, facilitate the development of broadly protective vaccines and antiviral therapeutics.
This page was last updated on 6/7/2013.