Much of what we know about poxvirus innate immune evasion comes from work with the prototype orthopoxvirus, vaccinia virus (VACV). However, it is becoming clear that what we know for VACV is not always true for other poxviruses. The example we have been working on is monkeypox virus (MPXV). VACV has an E3L gene, which is essential for interferon-resistance, both in cells in culture and in the animal model. Despite being highly pathogenic, MPXV is missing 37 residues from the N-terminus of its E3 homologue. Thus, it is surprising that MPXV is as pathogenic as it is, despite missing this essential region of the E3 innate immune evasion protein. We have shown that while the lack of an N-terminal innate immune evasion domain in MPXV allows the virus to be sensed by the host, MPXV has evolved at least two apparently independent mechanisms to overcome the effects of being sensed in cells. The goals of this research are to understand how this unique human pathogen is sensed in infected cells and how it has evolved to counter the effects of sensing. Loss of this innate immune evasion domain makes vaccination against MPXV problematic. The final goal of this project is to develop a vaccine that can safely protect against MPXV infection.

Public Health Relevance

The World Health Organization has identified monkeypox virus as the most important orthopoxvirus infection in humans after eradication of smallpox. Zoonotic monkeypox virus disease in Africa appears to be occurring more frequently in recent years, perhaps due to the cessation of smallpox vaccination. The work described in this proposal will aid in identifying treatments for monkeypox virus infections and in identifying safe vaccination regimens for preventing spread of monkeypox virus.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
Project #
Application #
Study Section
Virology - A Study Section (VIRA)
Program Officer
Natarajan, Ramya
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Arizona State University-Tempe Campus
Other Health Professions
Organized Research Units
United States
Zip Code
Jancovich, James K; Chapman, Dave; Hansen, Debra T et al. (2018) Immunization of Pigs by DNA Prime and Recombinant Vaccinia Virus Boost To Identify and Rank African Swine Fever Virus Immunogenic and Protective Proteins. J Virol 92:
Meador, Lydia R; Kessans, Sarah A; Kilbourne, Jacquelyn et al. (2017) A heterologous prime-boosting strategy with replicating Vaccinia virus vectors and plant-produced HIV-1 Gag/dgp41 virus-like particles. Virology 507:242-256
Koehler, Heather; Cotsmire, Samantha; Langland, Jeffrey et al. (2017) Inhibition of DAI-dependent necroptosis by the Z-DNA binding domain of the vaccinia virus innate immune evasion protein, E3. Proc Natl Acad Sci U S A 114:11506-11511
Huynh, Trung P; Jancovich, James K; Tripuraneni, Latha et al. (2017) Characterization of a PKR inhibitor from the pathogenic ranavirus, Ambystoma tigrinum virus, using a heterologous vaccinia virus system. Virology 511:290-299
Arndt, William D; White, Stacy D; Johnson, Brian P et al. (2016) Monkeypox virus induces the synthesis of less dsRNA than vaccinia virus, and is more resistant to the anti-poxvirus drug, IBT, than vaccinia virus. Virology 497:125-135
McAfee, Megan S; Huynh, Trung P; Johnson, John L et al. (2015) Interaction between unrelated viruses during in vivo co-infection to limit pathology and immunity. Virology 484:153-62
Arndt, William D; Cotsmire, Samantha; Trainor, Kelly et al. (2015) Evasion of the Innate Immune Type I Interferon System by Monkeypox Virus. J Virol 89:10489-99
Holechek, Susan A; Denzler, Karen L; Heck, Michael C et al. (2013) Use of a recombinant vaccinia virus expressing interferon gamma for post-exposure protection against vaccinia and ectromelia viruses. PLoS One 8:e77879
Wellensiek, Brian P; Larsen, Andrew C; Flores, Julia et al. (2013) A leader sequence capable of enhancing RNA expression and protein synthesis in mammalian cells. Protein Sci 22:1392-8
Wellensiek, Brian P; Larsen, Andrew C; Stephens, Bret et al. (2013) Genome-wide profiling of human cap-independent translation-enhancing elements. Nat Methods 10:747-50

Showing the most recent 10 out of 12 publications