Stan Lemon MD

EMAIL: smlemon@med.unc.edu

PERSONAL WEBSITE: https://unclineberger.org/directory/stanley-m-lemon/

PUBLICATIONS:

I have a longstanding interest in the mechanisms by which hepatotropic positive-strand RNA viruses replicate in the liver and cause diseases ranging from acute inflammatory hepatitis to cancer. My laboratory has focused on two viruses that are classified within different virus families, hepatitis A virus (HAV, a picornavirus) and hepatitis C virus (HCV, a flavivirus). Our past research has elucidated the structure and function of the 5’ and 3’ untranslated RNAs of these viruses, and among other accomplishments has identified the existence of conserved cis-acting RNA replication elements in picornaviruses, mapped the secondary structure and function of the internal ribosome entry sites (IRESs) of both HAV and HCV, and identified and characterized the unique host function of the microRNA, miR-122, in replication of HCV. Over the past two decades, my interests have evolved to include how these viral RNAs are recognized by host innate immune sensors, how HAV and HCV have evolved similar but also distinct mechanisms to evade antiviral defenses in the liver, and how these events influence inflammation and the development of immunity. More recently, we discovered that HAV is released noncytolytically from cells cloaked in host cell membranes, and circulates in the blood of infected humans in a quasi-enveloped form resistant to neutralizing anti-HAV antibodies. These seminal observations have blurred the classic distinctions between enveloped and non-enveloped viruses, thus challenging some basic, long held tenets of virology. The major projects currently being pursued in the laboratory focus on hepatitis A virology and mechanisms of pathogenesis, including HAV-induced liver injury and innate immune responses to HAV in a murine model of human hepatitis A, and in vitro studies of interactions between HAV proteins and ESCRT complexes required for HAV release as exosome-like quasi-enveloped virions; host factors required for cap-independent translation of HAV proteins, and changes in lipid metabolism resulting from and required for HAV infection.