The Amazing, Death Defying…Poxviruses

The Amazing, Death Defying…Poxviruses

November 7, 2018

Address

727 E. Tyler St.
Tempe, AZ 85281

Location

Biodesign Institute, Auditorium

Date and Time

November 14, 2018, 12:00 pm (Length: 1 hour 0 minutes)

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Bert Jacobs, PhD, Faculty Member, Biodesign Center for Immunotherapy, Vaccines and Virotherapy, Director and Professor, School of Life Sciences

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 necroptotic cell death. The cellular Z-NA binding protein, DAI, is essential for induction of necroptotic cell death in response to vaccinia virus infection, and Z-NA binding is essential to sense 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. Since many tumors have evolved to down-regulate the necroptotic pathway VACV E3 N-terminal mutants preferentially replicate in cancer cells, and may have utility as oncolytic viruses.