My laboratory studies the virology, immunology and therapy of HIV-1 and HBV persistent infection. We currently focus on viral factors that interact and counteract host innate anti-viral immunity, and on how human immune cells are dysregulated and contribute to diseases during HIV-1 and HBV infection. We have developed various mouse models including humanized mouse models with human immune and liver cells to study human immunopathology of chronic HIV-1 and HBV infection in vivo. Regarding HIV-1 infection, we currently focus on the HIV-1/pDC/IFN-I axis that plays a critical role in AIDS progression. We also study HBV virology and the HBV-Macrophage/stellate cell axis in HBV-induced liver diseases. In addition, we are developing novel immune modulatory therapeutics including antibodies, adjuvants and vaccines.
The HIV-pDC/IFN-I axis in hyper-inflammation, immune impairment and HIV-1 reservoir persistence
Plasmacytoid dendritic cells (pDC) are the major type I interferon (IFN-I) producing cells and play important roles in antiviral immune responses. However, HIV-1 induces sustained pDC activation and IFN-I induction, correlated with AIDS disease progression. We have recently defined how HIV-1 persistently activates the pDC-IFN axis, and studied the mechanisms of HIV/pDC/IFN-induced immune suppression, and its role in HIV-1 reservoir persistence and HIV cure therapy.
The HBV-Macrophage/stellate cell axis in HBV-induced liver diseases.
Chronic hepatitis B infection affects over 250 million individuals, resulting in chronic liver inflammation, fibrosis/cirrhosis and hepatocellular carcinoma (HCC). The mechanisms of chronic HBV infection and immunopathogenesis are poorly understood, and its therapeutic option is limited, due to a lack of relevant robust animal models. We have developed novel HBV models including humanized mouse models with both human immune system and human liver cells (Hu-HSC/Hep mice). The Hu-HSC/Hep mouse supports persistent HBV infection, leading to human-specific liver inflammation and fibrosis/cirrhosis in the chimeric liver. We show that HBV-infection induces M2-like human macrophages, correlated with human liver fibrosis in humanized mice and in chronic HBV-infected patients. The humanized mice with both human immune and liver cells provide a valuable in vivo platform for studying HBV infection, human immune responses and associated liver diseases, as well as for developing novel therapeutics targeting viral and host factors.
Cheng L, et al. 2017. Blocking type I interferon signaling enhances T cell recovery and reduces HIV-1 reservoirs. J Clin Invest. 127(1):269-279.
Ye C, et al. 2017. Glycosylphosphatidylinositol-Anchored Anti-HIV scFv Efficiently Protects CD4 T Cells from HIV-1 Infection and Deletion in hu-PBL Mice. J Virol. 18;91(3).
Li F, Nio K, Yasui F, Murphy CM, Su L. 2017. Studying HBV Infection and Therapy in Immune-Deficient NOD-Rag1-/-IL2RgammaC-null (NRG) Fumarylacetoacetate Hydrolase (Fah) Knockout Mice Transplanted with Human Hepatocytes. Methods Mol Biol. 1540:267-276.
Zhai N, et al. 2017. Hepatitis C Virus Induces MDSCs-Like Monocytes through TLR2/PI3K/AKT/STAT3 Signaling. PLoS One. 12(1):e0170516.
CCR5 interaction with HIV-1 Env contributes to Env-induced depletion of CD4 T cells in vitro and in vivo. Tsao LC, Guo H, Jeffrey J, Hoxie JA, Su L. 2016. Retrovirology. 13:22.
Guo H, et al. 2016. NLRX1 Sequesters STING to Negatively Regulate the Interferon Response, Thereby Facilitating the Replication of HIV-1 and DNA Viruses. Cell Host Microbe. 19(4):515-28.
Murphy CM, et al. 2016. Hepatitis B Virus X Protein Promotes Degradation of SMC5/6 to Enhance HBV Replication. Cell Rep. 16(11):2846-54.
Li F, et al. 2016. Minicircle HBV cccDNA with a Gaussia luciferase reporter for investigating HBV cccDNA biology and developing cccDNA-targeting drugs. Sci Rep. 6:36483.
Bility MT, et al. 2016. Chronic hepatitis C infection-induced liver fibrogenesis is associated with M2 macrophage activation. Sci Rep. 6:39520.
Zhang Q, et al. 2016. HCV core protein inhibits polarization and activity of both M1 and M2 macrophages through the TLR2 signaling pathway. Sci Rep. 6:36160.
Zhu D, et al. 2016. Clearing Persistent Extracellular Antigen of Hepatitis B Virus: An Immunomodulatory Strategy To Reverse Tolerance for an Effective Therapeutic Vaccination. J Immunol. 196(7):3079-87.
Pang X, et al. 2016; IL-10 plays a central regulatory role in the cytokines induced by hepatitis C virus core protein and polyinosinic acid:polycytodylic acid. Int Immunopharmacol. 38:284-290.
Brezar V, et al. 2016; T-Regulatory Cells and Vaccination “Pay Attention and Do Not Neglect Them”: Lessons from HIV and Cancer Vaccine Trials. Vaccines. 4(3). Review.
Zhang Z, et al. 2015. Plasmacytoid dendritic cells promote HIV-1-induced group 3 innate lymphoid cell depletion. J Clin Invest. 125(9):3692-703.
Reszka-Blanco NJ, Sivaraman V, Zhang L, Su L. 2015; HIV-1 Env and Nef Cooperatively Contribute to Plasmacytoid Dendritic Cell Activation via CD4-Dependent Mechanisms. J Virol. 89(15):7604-11.
Guo H, et al. 2015; SCARB2/LIMP-2 Regulates IFN Production of Plasmacytoid Dendritic Cells by Mediating Endosomal Translocation of TLR9 and Nuclear Translocation of IRF7. Journal of immunology 194(10):4737-49.
Wang Y, et al. 2015; Ribavirin Contributes to Hepatitis C Virus Suppression by Augmenting pDC Activation and Type 1 IFN Production. PLoS One. 10(8):e0135232.
Cheng M, et al. 2015. Characterization of species-specific genes regulated by E2-2 in human plasmacytoid dendritic cells. Sci Rep. 5:10752.
Whitehurst CB, et al. (2015) Knockout of Epstein-Barr virus BPLF1 retards B-cell transformation and lymphoma formation in humanized mice. MBio. 6(5):e01574-15. PMID: 26489865
Cheng L, Li F, Bility MT, Murphy CM, Su L. 2015; Modeling hepatitis B virus infection, immunopathology and therapy in mice. Antiviral Res 121:1-8. Review.
Robbins GR, et al. (2015) Analysis of human innate immune responses to PRINT fabricated nanoparticles with cross validation using a humanized mouse model. Nanomedicine. pii: S1549-9634(15)00004-0.
Li G, et al. 2014; Plasmacytoid dendritic cells suppress HIV-1 replication but contribute to HIV-1 induced immunopathogenesis in humanized mice. PLoS Pathog. 10(7):e1004291.
Guo H, et al. 2014; HIV-1 infection induces interleukin-1β production via TLR8 protein-dependent and NLRP3 inflammasome mechanisms in human monocytes. J Biol Chem. 289(31):21716-26.
Nunoya J, Washburn ML, Kovalev GI, Su L. 2014; Regulatory T cells prevent liver fibrosis during HIV type 1 infection in a humanized mouse model. J Infect Dis. 209(7):1039-44.
Bility MT, et al. 2014; Hepatitis B virus infection and immunopathogenesis in a humanized mouse model: induction of human-specific liver fibrosis and M2-like macrophages. PLoS Pathog. 10(3):e1004032.
Li F, et al. (2014) Efficient genetic manipulation of the NOD-Rag1-/-IL2RgammaC-null mouse by combining in vitro fertilization and CRISPR/Cas9 technology. Sci Rep. 4:5290.
Yang D, et al. 2014; A mouse model for HBV immunotolerance and immunotherapy. Cell Mol Immunol. 11(1):71-8.
Cheng L, et al. 2014; Hyper-IL-15 suppresses metastatic and autochthonous liver cancer by promoting tumour-specific CD8+ T cell responses. J Hepatol. 61(6):1297-303.
Chen Y, et al. (2014) Interferon-inducible cholesterol-25-hydroxylase inhibits hepatitis C virus replication via distinct mechanisms. Sci Rep. 4:7242.
Cheng L, et al. (2014) Immunotherapy of metastatic and autochthonous liver cancer with IL-15/IL-15Rα fusion protein. Oncoimmunology. 3(11):PMID: 25941592
Department of Microbiology & Immunology
Lineberger Comprehensive Cancer Center (LCCC)
Center for AIDS Research (CFAR)
Center for HIV/STDs and Infectious Disease (CFID)
Genetics and Molecular Biology
Interdisciplinary Program in Biomedical Sciences