My current research interests include mainly two areas: 1) HIV pathogenesis and 2) immunotherapy for curing HIV and cancer. To understand HIV pathogenesis, I mainly focus on the early events of viral infection in mucosal associated lymph tissues, which may have critical implications for prevention and cure. In recent years, we found that human cytomegalovirus latent infection modulates HIV-1 restriction factors in CD34+ hematopoietic stem cells (Blood Advances 2017). HIV-induced gut-homing Vd2 T cells upregulate isoformic PD-1 (Δ42PD-1) expression, leading to TLR4-mediated inflammation and acute mucosal damage (Nature Microbiology 2017). Meantime, we found that HIV-infected gut-homing CD4 T cells upregulate CCR7 expression by TGF-b, implicating their lymph node homing and latency established in central memory T cells (Journal of Virology 2018). Moreover, we recently found that blocking gut-homing CD4 T cells by a4b7-specific antibody is not sufficient to prevent HIV rebound after stopping antiretroviral treatment in humanized mice (AIDS 2019). These studies also establish platforms for evaluation of HIV immunotherapy. To investigate HIV immunotherapeutic cure, we have developed three HKU-patented technologies including PD1-based vaccine (JCI 2013, Cancer Res. 2014), tandem bi-specific antibody (JCI 2018) and anti-Δ42PD1 antibody drug (mAbs 2015). These publications have built a solid foundation for conducting our ongoing study on PD1 vaccine-based combination immunotherapy for a prolonged HIV control by potentiating host immunity. It should be noted that we are also very interested in applying our knowledge for cancer immunotherapy (Gut 2018, Oncoimmunology 2019). We, therefore, are fully committed to find solutions to end AIDS and cancer based on scientific discoveries..
Chen Z, Telfer P, Reed P, Zhang L, Getti A, Ho DD and Marx PA. Isolation and characterization of the first simian immunodeficiency virus from a feral sooty mangabey (Cercocebus atys) in West Africa. Journal of Medical Primatology. 24:108-115, 1995. (IF: 1.3; Cited: 45.)
Chen Z, Telfer P, Gettie A, Reed P, Zhang L, Ho DD and Marx PA. 1996. Genetic characterization of new West African simian immunodeficiency virus SIVsm: geographic clustering of household-derived SIV strains with human immunodeficiency virus type 2 subtypes and genetically diverse viruses from a single feral sooty mangabey troop. Journal of Virology 70:3617-3627, 1996.
Chen Z, Luckay A, Sodora DL, Telfer P, Reed P, Gettie A, Kanu JM, Sadek RF, Yee J, Ho DD, Zhang L and Marx PA. Human immunodeficiency virus type 2 (HIV-2) seroprevalence and characterization of a distinct HIV-2 genetic subtype from the natural range of simian immunodeficiency virus infected sooty mangabeys. Journal of Virology 71:3953-3960, 1997.
Chen Z, Zhou P, Ho DD, Landau NR and Marx PA. Genetically divergent strains of simian immunodeficiency virus use CCR5 as a coreceptor for entry. Journal of Virology 71:2705-2714, 1997.
Chen Z, Gettie A, Ho DD and Marx PA. Primary SIVsm isolates use the CCR5 co-receptor from sooty mangabeys naturally infected in West Africa: a comparison of coreceptor usage of primary SIVsm, HIV-2 and SIVmac. Virology 246:113-124, 1998.
Marx PA and Chen Z. The function of simian chemokine receptors in the replication of SIV. Seminars in Immunology (Invited review article) 10:215-223, 1998.
Chen Z, Kwon D, Jin Z , Monard S, Telfer P, Jones MS, Aguilar R, Ho DD and Marx PA. Natural infection of a homozygous deleted CCR5 red-capped mangabey with a CCR2b-tropic simian immunodeficiency virus. Journal of Experimental Medicine, Dec 7;188(11):2057-65, 1998.
Chen Z, Huang Y, Zhao X, Skulsky E, Lin D, Ip J, Gettie A and Ho DD. Enhanced infectivity of an R5-tropic simian/human immunodeficiency virus carrying human immunodeficiency virus type 1 subtype C envelope after serial passages in pig-tailed macaques (Macaca nemestrina). Journal of Virology 74:6501-10, 2000.
Chen Z, Zhao X, Huang Y, Huang YL, Gettie A, Ba L, Blanchard J and Ho DD. CD4+ Lymphocytopenia in Acute Infection of Asian Macaques by a Vaginally Transmissible Subtype-C, CCR5-Tropic Simian/Human Immunodeficiency Virus (SHIV). JAIDS. 30:133-145, 2002.
Su B, Liu L, Wang F, Gui X, Zhao M, Tien P, Zhang L and Chen Z*. HIV-1 subtype B’ dictates the AIDS epidemic among paid blood donors in the Henan and Hubei provinces of China. AIDS. 21;17(17):2515-20. 2003.
Wu Z, Chen Z, Phillips DM. Human genital epithelial cells capture cell-free human immunodeficiency virus type 1 and transmit the virus to CD4+ Cells: implications for mechanisms of sexual transmission. J Infect Dis. 188(10):1473-82. 2003.
Zhang L, Chen Z, Cao Y, Yu J, Li G, Yu W, Yin N, Mei S, Li L, Balfe P, He T, Ba L, Zhang F, Lin HH, Yuen MF, Lai CL, Ho DD. Molecular characterization of human immunodeficiency virus type 1 and hepatitis C virus in paid blood donors and injection drug users in china. Journal of Virology. 78(24):13591-9. 2004. (Shared the first author).
Chen Z*, Zhang L, Qin C, Ba L, Yi CE, Zhang F, Wei Q, He T, Yu W, Yu J, Gao H, Tu X, Gettie A, Farzan M, Yuen KY, Ho DD. Recombinant modified vaccinia virus Ankara expressing the spike glycoprotein of severe acute respiratory syndrome coronavirus induces protective neutralizing antibodies primarily targeting the receptor binding region. Journal of Virology. 79(5):2678-88. 2005.
Fang Q, Yang L, Zhu W, Liu L, Wang H, Yu W, Xiao G, Tien P, Zhang L, Chen Z*. Host range, growth property, and virulence of the smallpox vaccine: vaccinia virus Tian Tan strain. Virology. 10;335(2):242-51. 2005.
Yi CE, Ba L, Zhang L, Ho DD, Chen Z*. Single amino acid substitutions in the severe acute respiratory syndrome coronavirus spike glycoprotein determine viral entry and immunogenicity of a major neutralizing domain. Journal of Virology. Sep;79(18):11638-46. 2005.
Zhang Y, Lu L, Ba L, Liu L, Yang L, Jia M, Wang H, Fang Q, Shi Y, Yan W, Chang G, Zhang L, Ho DD, Chen Z*. Dominance of HIV-1 subtype CRF01_AE in sexually acquired cases leads to a new epidemic in Yunnan province of China. PLoS Medicine. 2006 Nov;3(11):e443.
Liu L, Fang Q, Deng F, Wang H, Yi C, Ba L, Yu W, Lin RD, Li T, Hu ZH, Ho DD, Zhang L, Chen Z*. Natural mutations in the receptor binding domain of spike glycoprotein determine the reactivity of cross-neutralization between palm civet coronavirus and severe acute respiratory syndrome coronavirus. Journal of Virology. 2007. May;81(9):4694-700.
Chen Z, Huang Y, Zhao X, Ba L, Zhang W and Ho DD. Design, Construction, and Characterization of a Multigenic Modified Vaccinia Ankara Candidate Vaccine against Human Immunodeficiency Virus Type 1 Subtype C/B’. JAIDS. 2008 Apr 1;47(4):412-21.
Huang Y, Chen Z, Zhang W, Song Y, Zhao X, Gardiner DF and Ho DD. Design, Construction, and Characterization of a Dual-Promoter Multigenic DNA Vaccine Directed against an HIV-1 Subtype C/B’ Recombinant. JAIDS. 2008 Apr 1;47(4):403-11.
Luo M, Liu H, Zhuang K, Liu L, Su B, Yang R, Tien P, Zhang L, Gui X and Chen Z*. Prevalence of drug resistant HIV-1 in rural areas of Hubei province in the People’s Republic of China. JAIDS. Jan 1; 50(1): 1-8. 2009.
Cheng S, LI J, Lin B, Lee D, Liu L, Chen Z, Lau A. HIV-1 trans-activator protein induction of suppressor of cytokine signaling-2 contributes to dysregulation of IFN signaling. Blood. 2009 May 21;113(21):5192-201.
Xue H, Lu XF, Zheng PR, Liu L, Han CY, Hu JP, Liu ZJ, Ma T, Li Y, Wang L, Chen Z* and Liu G*. Highly suppressing wild-type HIV-1 and Y181C Mutant HIV-1 Strains by 10-Chloromethyl-11-demethyl-12-oxo-calanolide A with druggable profile. Journal of Medicinal Chemistry. 53(3), pp1397-1401. 2010.
Yu W, Fang Q, Zhu W, Wang H, Tien P, Zhang L, and Chen Z*. One time intranasal vaccination with a modified vaccinia Tiantan strain MVTT (ZCI) protects animals against pathogenic viral challenge. Vaccine. 2010 Feb 25;28(9):2088-96.
Wang H, Zhuang K, Liu L, Tang Z, Tang J, Tien P, Zhang L, and Chen Z*. Acute infection of Chinese macaques by a CCR5-tropic SHIV carrying a primary HIV-1 subtype B’ envelope. JAIDS. 2010 Mar 1:53(3):285-291.
Liu L, Wei Q, Alvarez X, Wang H, Du Y, Zhu H, Jiang H, Zhou J, Lam P, Zhang L, Lackner A, Qin C, Chen Z*. Epithelial Cells Lining Salivary Gland Ducts Are Early Target Cells of Severe Acute Respiratory Syndrome Coronavirus Infection in the Upper Respiratory Tract of Rhesus Macaques. Journal of Virology. 2011. 85(8b):4025-4030.
Lu X, Liu L, Zhang X, Lau TC, Tsui SK, Kang Y, Zheng P, Zheng B, Liu G, Chen Z*. F18, a novel small molecule NNRTI, inhibits HIV-1 replication using distinct binding motifs as demonstrated by resistance selection and docking analysis. Antimicrob Agents Chemother. 2012 Jan;56(1):341-51
Yao X, Wang H, Yan P, Lu Y, Lin H, Chen L, Ng J, Lau E, Li L, Wu J, Chen Z*. Rising epidemic of HIV-1 infections among general populations in Fujian, China. JAIDS. 2012 Jul 1; 60(3): 328-35. (*corresponding author)
Kang Y, Wu Z, Lau TC, Lu X, Liu L, Cheung AK, Tan Z, Ng J, Liang J, Wang H, Li S, Zheng B, Li B, Chen L, Chen Z*. CCR5 antagonist TD-0680 uses a novel mechanism for enhanced potency against HIV-1 entry, cell-mediated infection, and a resistant variant. J Biol Chem. 2012 May 11;287(20):16499-509.
Kang Y, Guo J and Chen Z*. Closing the door to human immunodeficiency virus. Protein & Cell. 2013 4(2):86-102.
Sun C, Chen Z*, Tang X, Zhang Y, Feng L, Du Y, Xiao L, Liu L, Chen L, Zhang L*. Mucosal Prime with a Replicating Vaccinia-based Vaccine Elicits Protective Immunity against SIV Challenge in Rhesus Monkeys. Journal of Virology. 2013 May;87(10):5669-77.
Zhou J, Cheung AKL, Tan Z, Wang H, Kang Y, Du Y, Lu X, Liu L, Yuen KY and Chen Z*. sPD1-based DNA vaccine amplifies HIV-1 CD8+ T cells in mice. Journal of Clinical Investigation. 2013 Jun 3;123(6):2629-42.
Zhou J, Cheung AKL, Liu H, Tan Z, Tang X, Kang Y, Du Y, Wang H, Liu L, and Chen Z*. Potentiating functional antigen-specific CD8+ T cell immunity by a novel PD1 isoform-based fusion DNA vaccine. Mol Ther. 2013 Jul;21(7):1445-55.
Peng Q, Wang H, Wang HB, Li X, Lu X, Zhou B, and Chen Z* Imbalances of gut-homing CD4+ T cell subsets in HIV-1 infected Chinese patients. JAIDS. 2013 Sep 1;64(1):25-31.
Tan Z, Zhou J, Cheung AK, Yu Z, Cheung KW, Liang J, Wang H, Lee BK, Man K, Liu L, Yuen KY, Chen Z*. Vaccine-elicited CD8+ T cells cure mesothelioma by overcoming tumor-induced immunosuppressive environment. Cancer Res. 2014 Nov 1;74(21):6010-21.
Guo J, Zuo T, Cheng L, Wu X, Tang J, Sun C, Feng L, Chen L, Zhang L, Chen Z*. Simian immunodeficiency virus infection evades vaccine-elicited antibody responses to V2 region. JAIDS. 2015 Apr 15;68(5):502-10.
Cheng L, Tang X, Liu L, Peng J, Nishiura K, Cheung AK, Guo J, Wu X, Tang HY, An M, Zhou J, Cheung KW, Wang H, Guan X, Wu Z, Chen Z*. Monoclonal antibodies specific to human Δ42PD1: A novel immunoregulator potentially involved in HIV-1 and tumor pathogenesis. MAbs. 2015 May 4;7(3):620-9.
Yu Z, Tan Z, Lee BK, Tang J, Wu X, Cheung KW, Lo NT, Man K, Liu L, Chen Z*. Antigen spreading-induced CD8+T cells confer protection against the lethal challenge of wild-type malignant mesothelioma by eliminating myeloid-derived suppressor cells. Oncotarget. 2015 Oct 20;6(32):32426-32438.
Liu L, Wei Q, Nishiura K, Peng J, Wang H, Midkiff C, Alvarez X, Qin C, Lackner A and Chen Z*. Spatiotemporal interplay of Severe Acute Respiratory Syndrome Coronavirus and respiratory mucosal Cells drives viral dissemination in Rhesus Macaques. Mucosal Immunology. 2015 Dec 9. doi: 10.1038/mi.2015.127.
Wu X, Liu L, Cheung KW, Wang H, Lu X, Cheung AK, Liu W, Huang X, Li Y, Chen ZW, Chen SM, Zhang T, Wu H, Chen Z*. Brain Invasion by CD4(+) T Cells Infected with a Transmitted/Founder HIV-1BJZS7 During Acute Stage in Humanized Mice. J Neuroimmune Pharmacol. 2016 Sep;11(3):572-83.
Wei Q, Liu L, Cong Z, Wu X, Wang H, Qin C, Molina P, Chen Z*. Chronic Δ(9)-Tetrahydrocannabinol Administration Reduces IgE(+)B Cells but Unlikely Enhances Pathogenic SIVmac251 Infection in Male Rhesus Macaques of Chinese Origin. J Neuroimmune Pharmacol. 2016 Sep;11(3):584-591.
Cheung AKL, Huang Y, Kwok HY, Chen M, Chen Z*. Latent human cytomegalovirus enhances HIV-1 infection in CD34+ progenitor cells. Blood Adv. 2017 Jan 16;1(5):306-318.
Cheung AKL, Kwok HY, Huang Y, Chen M, Mo Y, Wu X, Lam KS, Kong HK, Lau TCK, Zhou J, Li J, Cheng L, Kiat Lee B, Peng Q, Lu X, An M, Wang H, Shang H, Zhou B, Wu H, Xu A, Yuen KY, Chen Z*. Gut-homing Δ42PD1+Vδ2 T cells promote innate mucosal damage via TLR4 during acute HIV type 1 infection. Nat Microbiol. 2017 Oct;2(10):1389-1402.
Chen ZW, Liu L, Chen G, Cheung KW, Du Y, Yao X, Lu Y, Chen L, Lin X, Chen Z*. Surging HIV-1 CRF07_BC epidemic among recently infected men who have sex with men in Fujian, China. J Med Virol. 2018 Mar 25. doi: 10.1002/jmv.25072.
Cheung KW, Wu T, Ho SF, Wong YC, Liu L, Wang H, Chen Z*. α4β7+CD4+ Effector/Effector Memory T Cells Differentiate into Productively and Latently Infected Central Memory T Cells by Transforming Growth Factor β1 during HIV-1 Infection. Journal of Virology. 2018 Mar 28;92(8). pii: e01510-17. doi: 10.1128/JVI.01510-17.
Wu X, Guo J, Niu M, An M, Liu L, Wang H, Jin X, Zhang Q, Lam KS, Wu T, Wang H, Wang Q, Du Y, Li J, Cheng L, Tang HY, Shang H, Zhang L, Zhou P, Chen Z*. Tandem bispecific neutralizing antibody eliminates HIV-1 infection in humanized mice. Journal of Clinical Investigation. 2018 Apr 23. pii: 96764. doi: 10.1172/JCI96764.
Tan Z, Liu L, Chiu MS, Cheung KW, Yan CW, Yu Z, Lee BK, Liu W, Man K, Chen Z*.Virotherapy-recruited PMN-MDSC infiltration of mesothelioma blocks antitumor CTL by IL-10-mediated dendritic cell suppression. Oncoimmunology. 2018 Oct 16;8(1):e1518672.
Ling L, Tang X, Huang X, Li J, Wang H, Chen Z*. AAV-Vectored Fms-Related Tyrosine Kinase 3 Ligand Inhibits CD34+ Progenitor Cell Engraftment in Humanized Mice. J Neuroimmune Pharmacol. 2018 Dec;13(4):541-550.
Tang J, Cai Y, Liang J, Tan Z, Tang X, Zhang C, Cheng L, Zhou J, Wang H, Yam WC, Chen X, Wang H, Chen Z*. In vivo electroporation of a codon-optimized BERopt DNA vaccine protects mice from pathogenic Mycobacterium tuberculosis aerosol challenge. Tuberculosis (Edinb). 2018 Dec;113:65-75.
Liu L, Wei Q, Lin Q, Fang J, Wang H, Kwok HY, Tang, HY, Nishiura K, Peng J, Tan Z, Wu T, Cheung KW, Chan KH, Alvarez X, Qin C, Lackner A, Perlman S, Yuen KY, Chen Z*. Anti–spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection. JCIinsight. 2019 Feb 21;4(4). pii: 123158.
Ling L, Wu T, To KKW, Cheung KW, Lui KOL, Niu M, Lam KS, Wang CC, Li J, Wang H, Yuen KY, Chen Z*. Vedolizumab-mediated integrin α4β7 blockade does not control HIV-1SF162 rebound after combination antiretroviral therapy interruption in humanized mice. AIDS. 2019 Mar 15;33(4):F1-F12. doi: 10.1097/QAD.0000000000002149.