Yong-Hui Zheng
University of Illinois Chicago, IL·Microbiology & Immunology
Many of the most dangerous human viruses — HIV-1, influenza A, Ebola, and coronaviruses including SARS-CoV-2 and MERS — all enter cells using the same general tool: a spike protein on the virus surface that fuses the viral membrane with the cell's membrane. These so-called class I fusion proteins are built in a cell compartment called the endoplasmic reticulum and then shipped to the Golgi apparatus, the cell's processing and packaging hub, where they are finished.
- Fields
Microbiology & Immunology
Biochemistry
Biology
- Topics
envelope glycoprotein
gp160
E3 ubiquitin ligase
- Grants
- 1 known grant, through Apr 2028
What they work on
- Characterize how MARCH8, a membrane-anchored ubiquitin ligase, blocks maturation of the HIV-1 envelope protein gp160 during infection of primary human cells and human T cell lines, using RNA silencing and CRISPR/Cas9 knockout.
- Test whether MARCH8's ubiquitin-tagging activity, rather than destruction of the viral protein, is what prevents furin from cutting gp160 into its mature fusion-competent form.
- Identify MARCH8's cellular targets among 18 Golgi proteins selected by bioinformatic analysis, including glycosidases, glycosyltransferases, furin, the COG trafficking complex, and SNARE membrane-fusion proteins.
- Determine whether the same MARCH8-driven defects in sugar modification and proteolytic cutting extend to the fusion proteins of SARS-CoV-2, MERS, Ebola and influenza A, defining how broadly this antiviral mechanism applies.
More about the research
In the Golgi, sugar chains are trimmed and remodeled (N- and O-glycosylation) and the protein is usually cut by a cellular enzyme called furin. If any of these finishing steps fail, the virus cannot make infectious particles at all. This project investigates how one host defense protein sabotages that process, using HIV-1's envelope protein gp160 as its main test case.
Why it matters
A single cellular protein that disables the entry machinery of HIV-1, SARS-CoV-2, Ebola and influenza is an appealing starting point for broad-spectrum antivirals. Working out exactly which Golgi proteins MARCH8 acts on could reveal host steps that drugs might mimic or block, pointing toward countermeasures that work against multiple highly pathogenic viruses rather than one at a time.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Heinrich Gottlinger
University of Massachusetts Chan Medical School, MA·Microbiology & Immunology
Determine how ADAM10, a membrane-anchored protease incorporated into HIV-1 particles, affects virus infectivity and cell-to-cell transmission, including whether other cellular ADAM10 substrates contribute to the block.
Thomas Gallagher
Loyola University Chicago, IL·Microbiology & Immunology
Determine how mutations in the S2 fusion segment of the SARS-CoV-2 spike control the receptor-binding domain and its engagement with receptors, identifying specific variant substitutions that alter receptor reactivity and spike stability.
Yuan Chang
University of Pittsburgh, PA·Microbiology & Immunology
Visualize single molecules of Merkel cell polyomavirus Large T protein binding, assembling and starting to unwind viral DNA, using the LUMICKS C-Trap optical tweezers instrument.
The school
University of Illinois Chicago: 42 labs on PI Pages, $532M a year on research, 359 research doctorates a year.
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