Zheng Lab | Department of Microbiology and Immunology | University of Illinois College of Medicine

About Us Heading link

The Zheng Lab at the University of Illinois Chicago focuses on understanding how viruses interact with host cells, particularly in the context of viral entry and replication. Our research delves into the mechanisms by which class I viral fusion proteins, such as those from HIV-1, Ebola virus, and SARS-CoV-2, are processed and regulated within host cells. We investigate host factors like ER chaperones, ubiquitin ligases, and restriction factors that influence viral protein maturation and degradation. Additionally, our studies explore the role of cellular receptors and pathways, such as NPC1-mediated endocytosis, in facilitating or restricting viral entry. Through these investigations, we aim to uncover potential antiviral targets and contribute to the development of effective therapeutic strategies

Meet Dr. Zheng Heading link

Yong-Hui Zheng

Principal Investigator

Class I Fusion Protein Biosynthesis and Inhibition Heading link

Diagram of SARS-CoV-2 spike protein processing and host cell entry, showing key cellular compartments and regulatory proteins involved in viral fusion and infection.

HIV-1, influenza virus, Ebola virus, and SARS-CoV-2 produce class I fusion proteins to infect cells. The core structure of class I fusion proteins features trimeric hairpins with a central coiled-coil structure, which are produced from their polypeptide precursors after cleavage by furin. During this process, class I fusion proteins are targeted by different types of host factors. Currently, we are investigating how ER chaperones (calnexin, calreticulin, PDIA3) and class I α-mannosidases (such as MAN1B1) trigger class I fusion protein degradation via reticulophagy. In addition, we are investigating how MARCHF E3 ubiquitin ligases inhibit furin to block their maturation. Moreover, we are investigating how SERINC5 inactivates them and how SERINC5 is counteracted by HIV-1 Nef, MLV glycoGag, and EIAV S2 proteins. On the other hand, we are also investigating in addition to ACE2, TMPRSS2, and CTSL, how SARS-CoV-2 enters cells via Niemann-Pick C1 (NPC1) known as the Ebola virus receptor. These investigations will lead to broad antiviral mechanisms to inhibit these highly pathogenic human viruses.

Links Heading link

Our Publications Heading link

Publication list

Ahmad I, Zhang J, Li R, Su W, Liu W, Wu Y, Khan I, Liu X, Li LF, Li S, Zheng YH. Murine Leukemia Virus GlycoGag Antagonizes SERINC5 via ER-phagy Receptor RETREG1. BioRxiv, 2025, doi: https://doi.org/10.1101/2025.03.06.641798.
Su W, Ahmad I, Wu Y, Tang L, Khan I, Ye B, Liang J, Li S, Zheng YH. Furin Egress from the TGN is Regulated by Membrane-Associated RING-CH Finger Proteins (MARCHF) and Ubiquitin-Specific Protease 32 (USP32) via Nondegradable K33-Polyubiquitination. Adv Sci (Weinh) 2024 Jul 19; 11(35):e2403732.
Khan I, Li S, Tao L, Wang C, Ye B, Li H, Liu X, Ahmad I, Su W, Zhong G, Wen Z, Wang J, Hua RH, Ma A, Liang J, Wan XP, Bu ZG, Zheng YH. Tubeimosides are pan-coronavirus and filovirus inhibitors that can block their fusion protein binding to Niemann-Pick C1. Nat Commun. 2024 Jan 2;15(1):162.
Zhang J, Wang B, Gao X, Peng C, Shan C, Johnson SF, Schwartz RC, Zheng YH. RNF185 regulates proteostasis in Ebolavirus infection by crosstalk between the calnexin cycle, ERAD, and reticulophagy. Nat Commun. 2022 Oct 12;13(1):6007.
Wang B, Zhang J, Liu X, Chai Q, Lu X, Yao X, Yang Z, Sun L, Johnson SF, Schwartz RC, Zheng YH. Protein disulfide isomerases (PDIs) negatively regulate ebolavirus structural glycoprotein expression in the endoplasmic reticulum (ER) via the autophagy-lysosomal pathway. Autophagy. 2022 Oct;18(10):2350-2367.
Li S, Li R, Ahmad I, Liu X, Johnson SF, Sun L, Zheng YH. Cul3-KLHL20 E3 ubiquitin ligase plays a key role in the arms race between HIV-1 Nef and host SERINC5 restriction. Nat Commun. 2022 Apr 26;13(1):2242.
Chai Q, Li S, Collins MK, Li R, Ahmad I, Johnson SF, Frabutt DA, Yang Z, Shen X, Sun L, Hu J, Hultquist JF, Peterlin BM, Zheng YH. HIV-1 Nef interacts with the cyclin K/CDK13 complex to antagonize SERINC5 for optimal viral infectivity. Cell Rep. 2021 Aug 10;36(6):109514.
Qiu X, Eke IE, Johnson SF, Ding C, Zheng YH. Proteasomal degradation of human SERINC4: A potent host anti-HIV-1 factor that is antagonized by nef. Curr Res Virol Sci. 2020;1.
Yu C, Li S, Zhang X, Khan I, Ahmad I, Zhou Y, Li S, Shi J, Wang Y, Zheng YH. MARCH8 Inhibits Ebola Virus Glycoprotein, Human Immunodeficiency Virus Type 1 Envelope Glycoprotein, and Avian Influenza Virus H5N1 Hemagglutinin Maturation. mBio. 2020 Sep 15;11(5).
Zhang X, Shi J, Qiu X, Chai Q, Frabutt DA, Schwartz RC, Zheng YH. CD4 Expression and Env Conformation Are Critical for HIV-1 Restriction by SERINC5. J Virol. 2019 Jul 15;93(14).
Ahmad I, Li S, Li R, Chai Q, Zhang L, Wang B, Yu C, Zheng YH. The retroviral accessory proteins S2, Nef, and glycoMA use similar mechanisms for antagonizing the host restriction factor SERINC5. J Biol Chem. 2019 Apr 26;294(17):7013-7024.
Li S, Ahmad I, Shi J, Wang B, Yu C, Zhang L, Zheng YH. Murine Leukemia Virus Glycosylated Gag Reduces Murine SERINC5 Protein Expression at Steady-State Levels via the Endosome/Lysosome Pathway to Counteract SERINC5 Antiretroviral Activity. J Virol. 2019 Jan 15;93(2).
Shi J, Xiong R, Zhou T, Su P, Zhang X, Qiu X, Li H, Li S, Yu C, Wang B, Ding C, Smithgall TE, Zheng YH. HIV-1 Nef Antagonizes SERINC5 Restriction by Downregulation of SERINC5 via the Endosome/Lysosome System. J Virol. 2018 Jun 1;92(11).
Frabutt DA, Wang B, Riaz S, Schwartz RC, Zheng YH. Innate Sensing of Influenza A Virus Hemagglutinin Glycoproteins by the Host Endoplasmic Reticulum (ER) Stress Pathway Triggers a Potent Antiviral Response via ER-Associated Protein Degradation. J Virol. 2018 Jan 1;92(1).
Zhang X, Zhou T, Yang J, Lin Y, Shi J, Zhang X, Frabutt DA, Zeng X, Li S, Venta PJ, Zheng YH. Identification of SERINC5-001 as the Predominant Spliced Isoform for HIV-1 Restriction. J Virol. 2017 May 15;91(10).
Wang B, Wang Y, Frabutt DA, Zhang X, Yao X, Hu D, Zhang Z, Liu C, Zheng S, Xiang SH, Zheng YH. Mechanistic understanding of N-glycosylation in Ebola virus glycoprotein maturation and function. J Biol Chem. 2017 Apr 7;292(14):5860-5870.
Frabutt DA, Zheng YH. Arms Race between Enveloped Viruses and the Host ERAD Machinery. Viruses. 2016 Sep 19;8(9).

Publications Heading link

Join Our Lab Heading link

Post-Docs

We have multiple open positions to be filled soon. Please send your CV to Dr. Zheng.
Graduate Students

We welcome students from GEMS and MSTP programs to join our lab to pursue a PhD or MD/PhD. Students from these programs who are interested in our research projects please directly contact Dr. Zheng via email.
Undergraduates

We welcome undergraduate students who are interested in biomedical research to join our lab. Prior lab experience is not required but is a plus. Refer to the UIC Undergraduate Research Experience (URE) program for more details. Apply via URE or email Dr. Zheng.