Jennifer (Jenny) Hyde

Virus and host determinants of viral pathogenesis

Alphaviruses are arthropod-borne positive sense RNA viruses that cause significant human and veterinary disease. Due to their ability to evolve rapidly, alphaviruses are important emerging and re-emerging viruses that pose threats to human and animal health. 

In the Hyde lab we are interested in understanding how virus-host interactions contribute to and regulate pathogenesis of alphaviruses, as well as other positive-sense RNA (+ssRNA) viruses. In particular we are interested in understanding how viral RNA structure determines viral pathogenesis and regulates viral replication under a variety of conditions (e.g. different host species including mosquitoes and mammals, different temperatures, basal vs immune stimulated). We leverage comparisons of attenuated and pathogenic viruses (particularly Venezuelan equine encephalitis virus, VEEV) to define RNA structures and molecular mechanisms that contribute to emergence of pathogenic viruses. 

Current areas of research in the Hyde lab include:

• Identification and characterization of RNA structures that contribute to emergence of pathogenic alphaviruses
• Novel mechanisms of encephalitic alphavirus pathogenesis
• Impact of RNA structure on myeloid cell tropism and pathogenesis of encephalitic alphaviruses
• Viral RNA structure in host switching
• Biological roles of RNA conformers and RNA structure dynamics
• Antiviral functions of coronavirus genes
• Novel functions of host antiviral genes
   

Publications

https://www.ncbi.nlm.nih.gov/myncbi/jennifer.hyde.1/bibliography/public/

Hickson, S, Brekke, E, Schwerk J, Salukhe, N, Zaver, S, Woodward, J, Savan, R, Hyde JL. Sequence diversity in the 3’ untranslated region of alphavirus modulatesIFIT2-dependent restriction in a cell type dependent manner. Review Commons (in review), 2021.

Soveg FW, Schwerk J, Gokhale NS, Cerosaletti K, Smith JR, Pairo-Castineira E, Kell AM, Forero A, Zaver SA, Esser-Nobis K, Roby JA, Hsiang TY, Ozarkar S, Clingan JM, McAnarney ET, Stone AE, Malhotra U, Speake C, Perez J, Balu C, Allenspach EJ, Hyde JL, Menachery VD, Sarkar SN, Woodward JJ, Stetson DB, Baillie JK, Buckner JH, Gale M Jr, Savan R. Endomembrane targeting of human OAS1 p46 augments antiviral activity. Elife. 2021 Aug 3;10. doi: 10.7554/eLife.71047. PubMed PMID: 34342578.

Choi R, Zhou M, Shek R, Wilson JW, Tillery L, Craig JK, Salukhe IA, Hickson SE, Kumar N, James RM, Buchko GW, Wu R, Huff S, Nguyen TT, Hurst BL, Cherry S, Barrett LK, Hyde JL, Van Voorhis WC. High-throughput screening of the ReFRAME, Pandemic Box, and COVID Box drug repurposing libraries against SARS-CoV-2 nsp15 endoribonuclease to identify small-molecule inhibitors of viral activity. PLoS One. 2021;16(4):e0250019. doi: 10.1371/journal.pone.0250019. eCollection 2021. PubMed PMID: 33886614; PubMed Central PMCID: PMC8062000.

Schwerk J, Soveg FW, Ryan AP, Thomas KR, Hatfield LD, Ozarkar S, Forero A, Kell AM, Roby JA, So L, Hyde JL, Gale M Jr, Daugherty MD, Savan R. RNA-binding protein isoforms ZAP-S and ZAP-L have distinct antiviral and immune resolution functions. Nat Immunol. 2019 Dec;20(12):1610-1620. doi: 10.1038/s41590-019-0527-6. Epub 2019 Nov 18. PubMed PMID: 31740798; PubMed Central PMCID: PMC7240801.