Research Interests

The Yount laboratory aims to identify and characterize post-translational modifications on innate immune system proteins, with the goal of exploiting these enzymatic modifications to control immune functions.  Using chemical tools, mass spectrometry, and biochemical techniques, we have identified lipid modifications that control the activity of Toll-like receptors and the interferon-induced transmembrane protein (IFITM) family of antiviral proteins.  Our ongoing studies of IFITM3 have also uncovered its regulation by additional post-translational modifications including phosphorylation and ubiquitination.  This work has revealed mechanisms that govern IFITM3 cellular trafficking and turnover, and provides insight into the deleterious effects of an IFITM3 polymorphism present in the human population that increases susceptibility to severe influenza virus infections.  Our most recent efforts have identified the primary E3 ubiquitin ligase responsible for promoting IFITM3 degradation.  Targeting this enzyme leads to increased IFITM3 levels in cells and provides broad cellular resistance to multiple influenza virus strains.  We are continuing to explore how ubiquitination and other post-translational modifications can be manipulated for prevention or treatment of infections.   

Membership

Microbial Infection and Immunity (Primary Appointment)

Comprehensive Cancer Center

Recent Publications

• Zani A, Zhang L, Kenney A, McMichael TM, Kwiek JJ, Liu SL, and Yount JS. IFITMs Inhibit Cell Fusion Mediated by Trophoblast Syncytins. 2019. BioRxiv Preprint.  https://www.biorxiv.org/content/10.1101/713032v2
• Kenney AD, McMichael TM, Imas A, Chesarino NM, Zhang L, Dorn LE, Wu Q, Alfaour O, Amari F, Chen M, Zani A, Chemudupati M, Accornero F, Coppola V, Rajaram MVS^#, and Yount JS^#. IFITM3 protects the heart during influenza virus infection. Proceedings of the National Academy of Sciences.  2019. ^#Corresponding authors.
• Sharma A, McLaughlin RN, Basom RS, Kikawa C, OhAinle M, Yount JS, Emerman M, and Overbaugh J.  Macaque interferon-induced transmembrane proteins limit replication of SHIV strains in an envelope-dependent manner.  PLOS Pathogens. 2019.
• Chemudupati M, Kenney AD, Bonifati S, Zani A, McMichael TM, Wu L, and Yount JS.  From APOBEC to ZAP: Diverse Mechanisms Used by Cellular Restriction Factors to Inhibit Virus Infections.  Biochimica et Biophysica Acta – Molecular Cell Research.  2019.
• McMichael TM, Zhang Y, Kenney AD, Zhang L, Zani A, Lu M, Chemudupati M, Li J, and Yount JS. IFITM3 restricts human metapneumovirus infection.  Journal of Infectious Diseases.  2018.
• Zani A and Yount JS.  Antiviral protection by IFITM3 in vivo.  Current Clinical Microbiology Reports.  2018. 
• Chen S, Bonifati S, Qin Z, St. Gelais C, Kodigepalli KM, Barrett BS, Kim SH, Antonucci JM, Ladner KJ, Vuzovetsky O, Knecht KM, Xiong Y, Yount JS, Guttridge DC, Santiago ML, and Wu L.  SAMHD1 suppresses innate immune responses to viral infections and inflammatory stimuli by inhibiting the NF-kB and interferon pathways.  Proceedings of the National Academy of Sciences.  2018.
• McMichael TM, Zhang L, Chemudupati M, Hach JC, Kenney AD, Hang HC, and Yount JS.  Palmitoyltransferase ZDHHC20 Enhances IFITM3 S-Palmitoylation and Antiviral Activity. Journal of Biological Chemistry.   2017.
• Chesarino NM, Compton A, McMichael TM, Zhang L, Kenney A, Soewarna V, Doering R, Davis M, Schwartz O, and Yount JS.  IFITM3 requires an amphipathic helix for restriction of virus infections. EMBO Reports.  2017. 
• Seveau S, Turner J, Gavrilin M, Torrelles JB, Hall-Stoodley L, Yount JS, and Amer AO.  Checks and balances between the inflammasome and the autophagosome. Accepted at Journal of Molecular Biology.  2017.
• Kenney A, Dowdle JA, McMichael TM, Bozacca L, St. Gelais C, Panfill A, Schlesinger LS, Anderson MZ, Greene P, Lopez CB, Rosenberg B, Wu L, and Yount JS.  Human Genetic Determinants of Viral Diseases. Annual Review of Genetics.  2017. 
• McMichael TM, Chemudupati M, and Yount JS.  A balancing act between IFITM3 and IRF3.  Cellular and Molecular Immunology.  2017. 
• St. Gelais C, Kim SH, Ding L, Yount JS, Ivanov D, Spearman P, and Wu L.  A putative cyclin-binding motif in human SAMHD1 contributes to protein phosphorylation, localization and stability.  Journal of Biological Chemistry. 2016. 
• Compton A, Roy N, Porrot F, Billet A, Casartelli N, Yount JS, Liang C, and Schwartz O.  Natural mutations in IFITM3 modulate post-translational regulation and toggle antiviral specificity. EMBO Reports.  2016. 
• Antonucci J, St. Gelais C, de Silva S, Yount JS, Tang C, Ji X, Xiong Y, Kim B, and Wu L. RNase activity of SAMHD1 is not essential for HIV-1 restriction in cells. Nature Medicine.  2016.
• Percher A, Ramakrishnan S, Yuan X, Thinon E, Yount JS^#, and Hang HC^#.  Mass-tag labeling reveals site-specific and quantitative levels of protein S-fatty acylation. Proceedings of the National Academy of Science.  2016.  ^#Corresponding authors.
• Wang F, St. Gelais C, de Silva S, Zhang H, Geng Y, Shepard C, Kim B, Yount JS, Wu L.  Phosphorylation of mouse SAMHD1 regulates its restriction of human immunodeficiency virus type 1 infection, but not murine leukemia virus infection.  Virology.  2016. 
• Chesarino NC, McMichael TM, and Yount JS.  E3 ubiquitin ligase NEDD4 promotes influenza virus infection by decreasing levels of the antiviral protein IFITM3.  PLOS Pathogens.  2015. Interface Biology’s “Most Impactful Papers of 2015” (the Center includes more than 80 labs)
• Melvin, WJ, McMichael TM, Chesarino NC Hach JC, and Yount JS.  IFITMs from mycobacteria confer resistance to influenza virus when expressed in human cells.  Viruses. 2015.
• Chesarino NM, Hach JC, Chen JL, Zaro BW, Rajaram M, Turner J, Schlesinger LS, Pratt M, Hang HC, and Yount JS.  Chemoproteomics reveals Toll-like receptor fatty acylation. BMC Biology.  2014.
• Chesarino NC, McMichael TM, Hach JC, and Yount JS.  Phosphorylation of the antiviral protein IFITM3 dually regulates its endocytosis and ubiquitination. Journal of Biological Chemistry.  2014.
• St. Gelais C, Hach JC, DeSilva S, Yount JS, and Wu L.  Identification of cell cycle proteins interacting with human and mouse anti-retroviral protein SAMHD1. Journal of Virology.  2014.
• Hach JC, McMichael T, Chesarino N, and Yount JS.  Palmitoylation on conserved and non-conserved cysteines of murine IFITM1 regulates its stability and anti-influenza A virus activity.  Journal of Virology.  2013.

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