IMV Executive Assistant
tel. (612) 624-1926
fax. (612) 625-1108
18-242 Moos Tower
515 Delaware St. SE
Minneapolis, MN 55455
Ph.D., Tufts University, 1985
Virus-host interactions, viral entry, translational control in virus-infected cells, viral immune avoidance mechanisms
A major research focus in my laboratory is to understand viral and cellular determinants that control reovirus entry into host cells. Current dogma holds that early in infection by mammalian reoviruses, exposure to low pH and protease uncoats virions to intermediate subvirion particles (ISVPs).ISVPs have the capacity to penetrate cell membranes by virtue of exposure of the membranolytic protein mu 1. Joe Golden's research indicates that many cell lines and primary cells are unable to support reovirus replication. Infection with ISVPs results in a productive infection within 90% of the cell lines that are restrictive to viral infection. The fact that ISVPs and not virions can infect these restrictive cells indicates that the block in these cells is at the step of virion to ISVP conversion (uncoating). We are currently examining the nature of the block to uncoating present within these cells to understand the cellular and molecular determinants of virion entry.
We are also studying the spectrum of proteases that participate in reovirus virion entry. In L929 mouse fibroblast cells, cathepsin L, an acid-dependent, lysosomal cysteine protease, is required for virion uncoating. Loss of this protease causes cells to become restrictive to infection by virions but not ISVPs. Some evidence suggests that cells that lack cathepsin L are still able to support virion infection, presumably by using an alternative protease to facilitate uncoating. Ongoing work is aimed at identifying the specific protease(s) that facilitate reovirus entry in these cells.
We are investigating the fundamental question of how viral protein synthesis comes to predominate over cellular translation in virus-infected cells. Because a strain polymorphism in reovirus-induced host translational shutoff mapped to the gene encoding viral protein sigma 3 (a dsRNA-binding protein), it has long been hypothesized that the mechanism of shutoff in reovirus-infected cells required the activity of PKR. PKR is a dsRNA-activated eIF2a kinase. Active (phosphorylated) PKR phosphorylates eIF2alpha, halting translation initiation. It has been proposed that strain differences in sigma 3 expression, localization or activity regulate the activation state of PKR -and thus levels of translation- in infected cells.
'Wisc-e-sota', a Joint UMN-UW Virology Training Grant Symposium was first held on Friday, Sepbember 20th, 2013 at the Uniiversity of Wisconsin-La Crosse, Cartwright Center. This was the inaugural collaborative symposium of the NIH T32-supported virology training programs at the University of Wisconsin-Madison and the University of Minnesota-Twin Cities. Talks and poster sessions were presented by students, postdocs and faculty. The second UMN-UW Virology Training Grant Symposium will be held in the Fall 2014. Details to follow.
The 2014 IMV Symposium will be held on May 12, 2014 and Mark Denison (Vanderbilt) and Bert Semler (UC-Irvine) will be the Keynote Speakers. Click on the link below to register and submit abstracts.
Read about bacteriophage phi 29 and why it matters.
Explore nearly a century's worth of discovery in the field of virology at the University of Minnesota.
"This Week in Virology" from professor Vincent Racaniello.