Virus and host determinants of viral pathogenesis

The interferon (IFN) response is well-established to be a major determinant of pathogenesis in many viral systems. Not surprisingly, viruses have evolved many and diverse mechanisms to inhibit the IFN response and its downstream effector molecules (IFN stimulated genes; ISGs). Our goal is to identify and characterize interactions between viruses and host immune molecules (ISGs) that contribute to the development of pathogenesis. In particular, our research is focused on understanding how viral RNA functions to modulate these virus-host interactions, and aims to address questions such as:

• How do changes in viral RNA sequence and structure impact virus-host interactions and pathogenesis?
• How do changes in viral RNA impact nucleic acid sensing by the host?
• What is the molecular mechanism(s) of ISGs that impact viral pathogenesis?
• What mechanisms have viruses evolved to circumvent restriction by these host factors?

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.