Faculty Profile

Dr. Jennifer S. Spence, Ph.D.

Jennifer S. Spence, Ph.D.

Research Assistant Professor, Department of Microbiology & Immunology

Areas of Research: Entry mechanisms of enveloped viruses, virus-host interactions, innate immune proteins, intracellular trafficking

Professional Interests

My research centers on illuminating fundamental processes required for the entry of viruses into host cells. Live-cell microscopy is a primary driver of my work, which integrates biophysical, biochemical, and genetic elements for the granular study of early infection events. I am currently addressing specific mechanistic questions in two particular areas of virus-host interaction that can only be resolved by a live, in-cell approach.

  1. Antiviral mechanism and biology of intracellular innate immune proteins:
    Interferon-induced transmembrane (IFITM) proteins comprise a family of highly-conserved immune effectors that inhibit members of nearly every family of enveloped RNA viruses, as well as vaccinia and herpes simplex 1 viruses, nonenveloped reovirus, and M. tuberculosis. Critical aspects of IFITM mechanism and biology have long remained unaddressed due to the difficulty in labeling these tiny proteins for visualization. With an innovative bioorthogonal labeling approach in hand, I am investigating the means by which IFITMs exert their exceedingly broad antiviral activity.
  2. Functional studies of viral glycoprotein-mediated fusion:
    The process of viral fusion protein activation varies widely in complexity among enveloped viruses, and filovirus fusion has been especially challenging to unravel due to its sequential priming events. Ebola virus, once internalized via macropinocytosis, undergoes extensive processing by endosomal cysteine cathepsins to remove the distal glycan caps and mucin-like domains of each glycoprotein (GP) spike. Proteolysis reveals the receptor-binding site of the GP1 subunit, which can then interact with its intracellular receptor, Niemann-Pick C1 (NPC1). While initial proteolysis, NPC1 binding, and low pH are all critical for infection, none of these individual factors can elicit fusion peptide extension and fusion pore formation; the precise trigger for fusion remains unknown. Using quantitative single-particle studies, I am dissecting the differential requirements for each step in the fusion process.

Selected Publications

Fels JM, Spence JS, Bortz RB III, Bornholdt ZA, Chandran K. A hyperstabilizing mutation in the base of the Ebola virus glycoprotein acts at multiple steps to abrogate viral entry. mBio 10:e01408-19 (2019).

Spence JS, He R, Hoffmann HH, Thinon E, Das T, Rice CM, Peng T, Chandran K, Hang HC. IFITM3 directly engages and shuttles incoming virus particles to lysosomes. Nature Chemical Biology 15:259-68 (2019).

Zhao X, Howell KA, He S, Brannan JM, Wec AZ, Davidson E, Turner HL, Chiang CI, Lei L, Fels JM, Vu H, Shulenin S, Turonis AN, Kuehne AI, Liu G, Ta M, Wang Y, Sundling C, Xiao Y, Spence JS, Doranz BJ, Holtsberg FW, Ward AB, Chandran K, Dye JM, Qui X, Li Y, Aman MJ. Immunization-elicited broadly protective antibody reveals ebolavirus fusion loop as a site of vulnerability. Cell 169:891-904 (2017).

Spence JS, Krause TB, Mittler E, Jangra RK, Chandran K. Direct visualization of Ebola virus fusion triggering in the endocytic pathway. mBio 7:e01857-15 (2016).

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