Monkeypox virus and variola virus share about 95% homology, and cause similar diseases in humans. Yet one of the major determinants of orthopoxvirus virulence, the E3L gene, differs significantly between these two closely related viruses. The monkeypox virus homologue of the variola virus (and vaccinia virus) E3L gene, which is an important vaccinia virus innate immune evasion gene, is partially deleted. Since vaccinia virus, when expressing a similarly deleted E3L is attenuated in experimental animals, it is important to understand the role of this variant monkeypox virus innate immune evasion gene in replication and immune evasion of monkeypox virus. The research in this application will characterize the altered genes in monkeypox virus that are compensating for the partial deletion of the monkeypox virus E3L homologue. As such the work described in this application will provide important information on how monkeypox virus causes disease in animals and in humans. Since monkeypox virus is considered to be a re- emerging human public health concern, this research may provide the basis for development of better vaccines for protection against monkeypox virus infection in humans, and for the development of better treatments for people who do become infected with monkeypox virus.
Monkeypox virus has become a re-emerging human public health concern, since the eradication of smallpox led to the decision to halt vaccination that protected humans from monkeypox virus as well as smallpox. The research proposed in this application will investigate how monkeypox virus evades the host immune system, and will likely have direct relevance to decisions on use of anti-poxviral drugs to treat potential human cases of monkeypox.
|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|
|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|
|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|
Showing the most recent 10 out of 12 publications