Matthew Wiebe, Ph.D.

Professor

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In the Wiebe Lab we are curious about numerous aspects of pathogen-host interaction, and focus on what poxviruses can teach us about this topic.  Poxviruses dedicate at least a third of their large genomes to encoding proteins involved in interacting with the host, providing us with an example of how sophisticated a virus can be in altering host function.  Intriguingly, poxvirus genes are often similar to some host genes, allowing the virus to mimic the cell in some ways during infection.  We are fascinated with these examples of mimicry, and work to dissect whether the similar viral and host factors perform the same functions or not.  In many cases, we observe that the viral factor performs slightly differently, informing us about the ways that viruses can manipulate cells to favor their own replication.

Much of our research focuses on the vaccinia virus, which is a member of the poxvirus family and is closely related to smallpox and monkeypox viruses.  Vaccinia was given as a live vaccine against smallpox during the World Health Organization’s successful campaign to eradicate smallpox 30 years ago.Our research with vaccinia has led to the discovery that during replication of the viral DNA, vaccinia must evade a cellular protein called BAF, which would otherwise bind to the viral DNA and inhibit its replication.  The virus evades BAF by inactivating its DNA binding capability via phosphorylation of BAF by a viral kinase that is a mimic of cellular enzymes.  These studies indicate that BAF is a novel type of host defense against viral DNA, which may in fact extend to other sources of foreign DNA, including other viruses and potentially bacteria.  Furthermore, BAF is expressed in most cell types and thus is likely to be a general DNA-specific defense in a wide range of tissues.

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