BMSE Seminar: "The Amazing Death-defying.........Poxviruses"


Prof. Bertram Jacobs, Director of the School of Life Sciences, Arizona State University,Tempe Host: Chuck Samuel

Date and Location

Wednesday March 14, 2018 11:00am to 12:00pm
1601 Elings Hall


Poxviruses are amongst the most interferon-resistant viruses that have been characterized.  The vaccinia virus E3L gene is essential for interferon-resistance.  One of the main functions of E3L encoded proteins is to bind to and sequester the viral pathogen-associated molecular pattern (PAMP), A-form dsRNA. However, most poxvirus E3L–like genes encode a second nucleic acid binding domain, capable of recognizing Z-form nucleic acid.  Our recent data demonstrates that this Z-NA binding domain of E3 proteins is essential for interferon-resistance, by inhibiting pre-mature program necrotic cell death.  The cellular Z-NA binding protein, DAI, is essential for induction of necrotic cell death in response to vaccinia virus infection. Thus, vaccinia virus appears to induce Z-form nucleic acid as a PAMP, that is recognized by the cellular pattern recognition receptor, DAI.  The vaccinia virus E3 Z-NA binding domain inhibits induction of pre-mature programmed necrosis, presumably by binding to the virus induced Z-form nucleic acid PAMP.  The human pathogen, monkeypox virus, is one of the few chordopoxviruses that do not encode a fully functional Z-NA binding domain.  Monkeypox virus appears to have evolved mechanisms to partially prevent induction of programmed necrosis in infected cells.  Nonetheless, monkeypox virus induces increased pathogenesis in mice deficient in programmed necrosis. Thus, sequestering Z-form nucleic acid appears to be important for poxvirus-induced pathogenesis.