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Dr. Yuntao Wu is a professor in the National Center for Biodefense and Infectious Diseases at George Mason University. He has been studying viruses for over 30 years, and for the past 20 years, he has been primarily focused on studying HIV infection of blood CD4 T cells and macrophages. Dr. Wu received his Ph.D. in Molecular Virology from Queen’s University, Canada, and received his postdoctoral training at NIH, studying HIV-1 pre-integration transcription in blood resting CD4 T cells (Science, 2001, 293:1503). Currently, his lab studies chemokine co-receptor signaling and role of cofilin in HIV infection and pathogenesis (Cell, 2008, 134:782; Science Advances, 2019, 5:eaat7911). Recently, his lab also studies the mechanisms of PSGL-1 restriction of HIV infectivity (Nature Microbiology, 2019, 4:8132; PNAS, 2020, 117:9537).
Background The ongoing global pandemic of coronavirus disease 2019 (COVID-19) has resulted in the infection of over 128 million people and has caused over 2.8 million deaths as of April 2021 in more than 220 countries and territories. Currently, there is no effective treatment for COVID-19 to reduce mortality. We investigated the potential anti-coronavirus activities from an oral liquid of traditional medicine, Respiratory Detox Shot (RDS), which contains mostly herbal ingredients traditionally used to manage lung diseases. Results Here we report that RDS inhibited the infection of target cells by lenti-SARS-CoV, lenti-SARS-CoV-2, and hybrid alphavirus-SARS-CoV-2 (Ha-CoV-2) pseudoviruses, and by infectious SARS-CoV-2 and derived Ha-CoV-2 variants including B.1.1.7, B.1.351, P.1, B.1.429, B.1.2, B.1.494, B.1.1.207, B.1.258, and B.1.1.298. We further demonstrated that RDS directly inactivates the infectivity of SARS-CoV-2 virus particles. In addition, we found that RDS can also block the infection of target cells by Influenza A virus. Conclusions These results suggest that RDS may broadly inhibit the infection of respiratory viruses.
Brian Hetrick; Dongyang Yu; Adeyemi A. Olanrewaju; Linda D. Chilin; Sijia He; Deemah Dabbagh; Ghaliah Alluhaibi; Yuan-Chun Ma; Lewis A. Hofmann; Ramin M. Hakami; Yuntao Wu. A traditional medicine, respiratory detox shot (RDS), inhibits the infection of SARS-CoV, SARS-CoV-2, and the influenza A virus in vitro. Cell & Bioscience 2021, 11, 1 -12.
AMA StyleBrian Hetrick, Dongyang Yu, Adeyemi A. Olanrewaju, Linda D. Chilin, Sijia He, Deemah Dabbagh, Ghaliah Alluhaibi, Yuan-Chun Ma, Lewis A. Hofmann, Ramin M. Hakami, Yuntao Wu. A traditional medicine, respiratory detox shot (RDS), inhibits the infection of SARS-CoV, SARS-CoV-2, and the influenza A virus in vitro. Cell & Bioscience. 2021; 11 (1):1-12.
Chicago/Turabian StyleBrian Hetrick; Dongyang Yu; Adeyemi A. Olanrewaju; Linda D. Chilin; Sijia He; Deemah Dabbagh; Ghaliah Alluhaibi; Yuan-Chun Ma; Lewis A. Hofmann; Ramin M. Hakami; Yuntao Wu. 2021. "A traditional medicine, respiratory detox shot (RDS), inhibits the infection of SARS-CoV, SARS-CoV-2, and the influenza A virus in vitro." Cell & Bioscience 11, no. 1: 1-12.
Mucins and mucin-like molecules are highly glycosylated, high-molecular-weight cell surface proteins that possess a semi-rigid and highly extended extracellular domain. P-selectin glycoprotein ligand-1 (PSGL-1), a mucin-like glycoprotein, has recently been found to restrict HIV-1 infectivity through virion incorporation that sterically hinders virus particle attachment to target cells. Here, we report the identification of a family of antiviral cellular proteins, named the Surface-Hinged, Rigidly-Extended Killer (SHREK) family of virion inactivators (PSGL-1, CD43, TIM-1, CD34, PODXL1, PODXL2, CD164, MUC1, MUC4, and TMEM123) that share similar structural characteristics with PSGL-1. We demonstrate that SHREK proteins block HIV-1 infectivity by inhibiting virus particle attachment to target cells. In addition, we demonstrate that SHREK proteins are broad-spectrum host antiviral factors that block the infection of diverse viruses such as influenza A. Furthermore, we demonstrate that a subset of SHREKs also blocks the infectivity of a hybrid alphavirus-SARS-CoV-2 (Ha-CoV-2) pseudovirus. These results suggest that SHREK proteins may be a part of host innate immunity against enveloped viruses.
Deemah Dabbagh; Sijia He; Brian Hetrick; Linda Chilin; Ali Andalibi; Yuntao Wu. Identification of the SHREK Family of Proteins as Broad-Spectrum Host Antiviral Factors. Viruses 2021, 13, 832 .
AMA StyleDeemah Dabbagh, Sijia He, Brian Hetrick, Linda Chilin, Ali Andalibi, Yuntao Wu. Identification of the SHREK Family of Proteins as Broad-Spectrum Host Antiviral Factors. Viruses. 2021; 13 (5):832.
Chicago/Turabian StyleDeemah Dabbagh; Sijia He; Brian Hetrick; Linda Chilin; Ali Andalibi; Yuntao Wu. 2021. "Identification of the SHREK Family of Proteins as Broad-Spectrum Host Antiviral Factors." Viruses 13, no. 5: 832.
Mucins and mucin-like molecules are highly glycosylated, high-molecular-weight cell surface proteins that possess a semi-rigid and highly extended extracellular domain. P-selectin glycoprotein ligand-1 (PSGL-1), a mucin-like glycoprotein, has recently been found to restrict HIV-1 infectivity through virion incorporation that sterically hinders virus particle attachment to target cells. Here, we report the identification of a family of antiviral cellular proteins, named the Surface-Hinged, Rigidly-Extended Killer (SHREK) family of virion inactivators (PSGL-1, CD43, TIM-1, CD34, PODXL1, PODXL2, CD164, MUC1, MUC4, and TMEM123), that share similar structural characteristics with PSGL-1. We demonstrate that SHREK proteins block HIV-1 infectivity by inhibiting virus particle attachment to target cells. In addition, we demonstrate that SHREK proteins are broad-spectrum host antiviral factors that block the infection of diverse viruses such as influenza A. Furthermore, we demonstrate that a subset of SHREKs also blocks the infectivity of a hybrid alphavirus-SARS-CoV-2 virus-like particle. These results suggest that SHREK proteins may be a part of host innate immunity against enveloped viruses.
Deemah Dabbagh; Sijia He; Brian Hetrick; Linda Chilin; Ali Andalibi; Yuntao Wu. Identification of the SHREK family of proteins as broad-spectrum host antiviral factors. 2021, 1 .
AMA StyleDeemah Dabbagh, Sijia He, Brian Hetrick, Linda Chilin, Ali Andalibi, Yuntao Wu. Identification of the SHREK family of proteins as broad-spectrum host antiviral factors. . 2021; ():1.
Chicago/Turabian StyleDeemah Dabbagh; Sijia He; Brian Hetrick; Linda Chilin; Ali Andalibi; Yuntao Wu. 2021. "Identification of the SHREK family of proteins as broad-spectrum host antiviral factors." , no. : 1.
P-selectin glycoprotein ligand-1 (PSGL-1) is a cell surface glycoprotein that binds to P-, E-, and L-selectins to mediate the tethering and rolling of immune cells on the surface of the endothelium for cell migration into inflamed tissues. PSGL-1 has been identified as an interferon-γ (INF-γ)-regulated factor that restricts HIV-1 infectivity, and has recently been found to possess broad-spectrum antiviral activities. Here we report that the expression of PSGL-1 in virus-producing cells impairs the incorporation of SARS-CoV and SARS-CoV-2 spike (S) glycoproteins into pseudovirions and blocks pseudovirus attachment and infection of target cells. These findings suggest that PSGL-1 may potentially inhibit coronavirus replication in PSGL-1+ cells
Sijia He; Abdul A. Waheed; Brian Hetrick; Deemah Dabbagh; Ivan V. Akhrymuk; Kylene Kehn-Hall; Eric O. Freed; Yuntao Wu. PSGL-1 Inhibits the Incorporation of SARS-CoV and SARS-CoV-2 Spike Glycoproteins into Pseudovirions and Impairs Pseudovirus Attachment and Infectivity. Viruses 2020, 13, 46 .
AMA StyleSijia He, Abdul A. Waheed, Brian Hetrick, Deemah Dabbagh, Ivan V. Akhrymuk, Kylene Kehn-Hall, Eric O. Freed, Yuntao Wu. PSGL-1 Inhibits the Incorporation of SARS-CoV and SARS-CoV-2 Spike Glycoproteins into Pseudovirions and Impairs Pseudovirus Attachment and Infectivity. Viruses. 2020; 13 (1):46.
Chicago/Turabian StyleSijia He; Abdul A. Waheed; Brian Hetrick; Deemah Dabbagh; Ivan V. Akhrymuk; Kylene Kehn-Hall; Eric O. Freed; Yuntao Wu. 2020. "PSGL-1 Inhibits the Incorporation of SARS-CoV and SARS-CoV-2 Spike Glycoproteins into Pseudovirions and Impairs Pseudovirus Attachment and Infectivity." Viruses 13, no. 1: 46.
SUMMARY Timely development of vaccines and antiviral drugs is critical to control the COVID-19 pandemic 1–6. Current methods for quantifying vaccine-induced neutralizing antibodies involve the use of pseudoviruses, such as the SARS-CoV-2 spike protein (S) pseudotyped lentivirus7–14. However, these pseudoviruses contain structural proteins foreign to SARS-CoV-2, and require days to infect and express reporter genes15. Here we describe the development of a new hybrid alphavirus-SARS-CoV-2 (Ha-CoV-2) particle for rapid and accurate quantification of neutralization antibodies and viral variants. Ha-CoV-2 is a non-replicating SARS-CoV-2 virus-like particle, composed of SARS-CoV-2 structural proteins (S, M, N, and E) and a RNA genome derived from a fast expressing alphavirus vector 16. We demonstrated that Ha-CoV-2 can rapidly and robustly express reporter genes in target cells within 3-6 hours. We further validated Ha-CoV-2 for rapid quantification of neutralization antibodies, viral variants, and antiviral drugs. In addition, as a proof-of-concept, we assembled and compared the relative infectivity of a panel of 10 Ha-CoV-2 variant isolates (D614G, P.1, B.1.1.207, B.1.351, B.1.1.7, B.1.429, B.1.258, B.1.494, B.1.2, B.1.1298), and demonstrated that these variants in general are 2-10 fold more infectious. Furthermore, we quantified the anti-serum from an infected and vaccinated individual; the one dose vaccination with Moderna mRNA-1273 has greatly increased the anti-serum titer for approximately 6 fold. The post-vaccination serum has also demonstrated various neutralizing activities against all 9 variants tested. These results demonstrated that Ha-CoV-2 can be used as a robust platform for rapid quantification of neutralizing antibodies against SARS-CoV-2 and its variants.
Brian Hetrick; Sijia He; Linda D. Chilin; Deemah Dabbagh; Farhang Alem; Aarthi Narayanan; Alessandra Luchini; Tuanjie Li; Xuefeng Liu; Joshua Copeland; Angela Pak; Tshaka Cunningham; Lance Liotta; Emanuel F. Petricoin; Ali Andalibi; Yuntao Wu. Development of a novel hybrid alphavirus-SARS-CoV-2 particle for rapid in vitro screening and quantification of neutralization antibodies, viral variants, and antiviral drugs. 2020, 1 .
AMA StyleBrian Hetrick, Sijia He, Linda D. Chilin, Deemah Dabbagh, Farhang Alem, Aarthi Narayanan, Alessandra Luchini, Tuanjie Li, Xuefeng Liu, Joshua Copeland, Angela Pak, Tshaka Cunningham, Lance Liotta, Emanuel F. Petricoin, Ali Andalibi, Yuntao Wu. Development of a novel hybrid alphavirus-SARS-CoV-2 particle for rapid in vitro screening and quantification of neutralization antibodies, viral variants, and antiviral drugs. . 2020; ():1.
Chicago/Turabian StyleBrian Hetrick; Sijia He; Linda D. Chilin; Deemah Dabbagh; Farhang Alem; Aarthi Narayanan; Alessandra Luchini; Tuanjie Li; Xuefeng Liu; Joshua Copeland; Angela Pak; Tshaka Cunningham; Lance Liotta; Emanuel F. Petricoin; Ali Andalibi; Yuntao Wu. 2020. "Development of a novel hybrid alphavirus-SARS-CoV-2 particle for rapid in vitro screening and quantification of neutralization antibodies, viral variants, and antiviral drugs." , no. : 1.
The ongoing global pandemic of coronavirus disease 2019 (COVID-19) has resulted in the infection of over 60 million people and has caused over 1.4 million deaths as of December 2020 in more than 220 countries and territories. Currently, there is no effective treatment for COVID-19 to reduce mortality. We investigated the potential anti-coronavirus activities from an oral liquid of traditional medicine, Respiratory Detox Shot (RDS), which contains mostly herbal ingredients traditionally used to manage lung diseases. Here we report that RDS inhibited the infection of target cells by SARS-CoV and SARS-CoV-2 pseudoviruses, and by infectious wild-type SARS-CoV-2. We further demonstrated that RDS inhibits viral early infection steps. In addition, we found that RDS can also block the infection of target cells by Influenza A virus. These results suggest that RDS may broadly inhibit the infection of respiratory viruses.
Brian Hetrick; Dongyang Yu; Adeyemi A. Olanrewaju; Linda D. Chilin; Sijia He; Deemah Debbagh; Yuan-Chun Ma; Lewis A. Hofmann; Ramin M. Hakami; Yuntao Wu. A traditional medicine, Respiratory Detox Shot (RDS), inhibits the infection of SARS-CoV, SARS-CoV-2, and the Influenza A virus in vitro. 2020, 1 .
AMA StyleBrian Hetrick, Dongyang Yu, Adeyemi A. Olanrewaju, Linda D. Chilin, Sijia He, Deemah Debbagh, Yuan-Chun Ma, Lewis A. Hofmann, Ramin M. Hakami, Yuntao Wu. A traditional medicine, Respiratory Detox Shot (RDS), inhibits the infection of SARS-CoV, SARS-CoV-2, and the Influenza A virus in vitro. . 2020; ():1.
Chicago/Turabian StyleBrian Hetrick; Dongyang Yu; Adeyemi A. Olanrewaju; Linda D. Chilin; Sijia He; Deemah Debbagh; Yuan-Chun Ma; Lewis A. Hofmann; Ramin M. Hakami; Yuntao Wu. 2020. "A traditional medicine, Respiratory Detox Shot (RDS), inhibits the infection of SARS-CoV, SARS-CoV-2, and the Influenza A virus in vitro." , no. : 1.
P-selectin glycoprotein ligand-1 (PSGL-1) is a cell surface glycoprotein that binds to P-, E-, and L-selectins to mediate the tethering and rolling of immune cells on the surface of the endothelium for cell migration into inflamed tissues. PSGL-1 has been identified as an interferon-γ (INF-γ)-regulated factor that restricts HIV-1 infectivity, and has recently been found to possess broad-spectrum antiviral activities. Here we report that the expression of PSGL-1 in virus-producing cells impairs the incorporation of SARS-CoV and SARS-CoV-2 spike (S) glycoproteins into pseudovirions and blocks virus attachment and infection of target cells. These findings suggest that PSGL-1 may potentially inhibit coronavirus replication in PSGL-1+ cells.
Sijia He; Abdul A. Waheed; Brian Hetrick; Deemah Dabbagh; Ivan V. Akhrymuk; Kylene Kehn-Hall; Eric O. Freed; Yuntao Wu. PSGL-1 inhibits the virion incorporation of SARS-CoV and SARS-CoV-2 spike glycoproteins and impairs virus attachment and infectivity. 2020, 1 .
AMA StyleSijia He, Abdul A. Waheed, Brian Hetrick, Deemah Dabbagh, Ivan V. Akhrymuk, Kylene Kehn-Hall, Eric O. Freed, Yuntao Wu. PSGL-1 inhibits the virion incorporation of SARS-CoV and SARS-CoV-2 spike glycoproteins and impairs virus attachment and infectivity. . 2020; ():1.
Chicago/Turabian StyleSijia He; Abdul A. Waheed; Brian Hetrick; Deemah Dabbagh; Ivan V. Akhrymuk; Kylene Kehn-Hall; Eric O. Freed; Yuntao Wu. 2020. "PSGL-1 inhibits the virion incorporation of SARS-CoV and SARS-CoV-2 spike glycoproteins and impairs virus attachment and infectivity." , no. : 1.
P-selectin glycoprotein ligand-1 (PSGL-1) is a dimeric, mucin-like, 120-kDa glycoprotein that binds to P-, E-, and L-selectins. PSGL-1 is expressed primarily on the surface of lymphoid and myeloid cells and is up-regulated during inflammation to mediate leukocyte tethering and rolling on the surface of endothelium for migration into inflamed tissues. Although it has been reported that PSGL-1 expression inhibits HIV-1 replication, the mechanism of PSGL-1–mediated anti-HIV activity remains to be elucidated. Here we report that PSGL-1 in virions blocks the infectivity of HIV-1 particles by preventing the binding of particles to target cells. This inhibitory activity is independent of the viral glycoprotein present on the virus particle; the binding of particles bearing the HIV-1 envelope glycoprotein or vesicular stomatitis virus G glycoprotein or even lacking a viral glycoprotein is impaired by PSGL-1. Mapping studies show that the extracellular N-terminal domain of PSGL-1 is necessary for its anti–HIV-1 activity, and that the PSGL-1 cytoplasmic tail contributes to inhibition. In addition, we demonstrate that the PSGL-1–related monomeric E-selectin–binding glycoprotein CD43 also effectively blocks HIV-1 infectivity. HIV-1 infection, or expression of either Vpu or Nef, down-regulates PSGL-1 from the cell surface; expression of Vpu appears to be primarily responsible for enabling the virus to partially escape PSGL-1–mediated restriction. Finally, we show that PSGL-1 inhibits the infectivity of other viruses, such as murine leukemia virus and influenza A virus. These findings demonstrate that PSGL-1 is a broad-spectrum antiviral host factor with a unique mechanism of action.
Yajing Fu; Sijia He; Abdul A. Waheed; Deemah Dabbagh; Zheng Zhou; Benjamin Trinité; Zhao Wang; Jieshi Yu; Dan Wang; Feng Li; David N. Levy; Hong Shang; Eric O. Freed; Yuntao Wu. PSGL-1 restricts HIV-1 infectivity by blocking virus particle attachment to target cells. Proceedings of the National Academy of Sciences 2020, 117, 9537 -9545.
AMA StyleYajing Fu, Sijia He, Abdul A. Waheed, Deemah Dabbagh, Zheng Zhou, Benjamin Trinité, Zhao Wang, Jieshi Yu, Dan Wang, Feng Li, David N. Levy, Hong Shang, Eric O. Freed, Yuntao Wu. PSGL-1 restricts HIV-1 infectivity by blocking virus particle attachment to target cells. Proceedings of the National Academy of Sciences. 2020; 117 (17):9537-9545.
Chicago/Turabian StyleYajing Fu; Sijia He; Abdul A. Waheed; Deemah Dabbagh; Zheng Zhou; Benjamin Trinité; Zhao Wang; Jieshi Yu; Dan Wang; Feng Li; David N. Levy; Hong Shang; Eric O. Freed; Yuntao Wu. 2020. "PSGL-1 restricts HIV-1 infectivity by blocking virus particle attachment to target cells." Proceedings of the National Academy of Sciences 117, no. 17: 9537-9545.
We have read with great interest the Correspondence by Shibo Jiang and colleagues,1Jiang S Shi Z Shu Y et al.A distinct name is needed for the new coronavirus.Lancet. 2020; (published online Feb 19.)https://doi.org/10.1016/S0140-6736(20)30419-0Summary Full Text Full Text PDF Scopus (77) Google Scholar in which they propose a name change for the newly emerged coronavirus,2Zhu N Zhang D Wang W et al.A novel coronavirus from patients with pneumonia in China, 2019.N Engl J Med. 2020; 382: 727-733Crossref PubMed Scopus (4265) Google Scholar which was recently designated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the Coronavirus Study Group of the International Committee on Taxonomy of Viruses.3Gorbalenya AE Baker SC Baric RS et al.Severe acute respiratory syndrome-related coronavirus: the species and its viruses - a statement of the Coronavirus Study Group.bioRxiv. 2020; (published online Feb 11.) (preprint).DOI: 10.1101/2020.02.07.937863Google Scholar The authors argued that the use of SARS in the virus name could confuse the public about the disease that it causes; in addition, they noted that the name SARS-CoV-2 is not consistent with the disease name chosen by WHO, coronavirus disease 2019. The authors also indicated that scientifically, SARS-CoV-2 is naturally occurring and different from other SARS-like or SARS-related coronaviruses that are mainly characterised by their genome sequences. Furthermore, given the probability of future attenuation of this virus to a low-pathogenic form, the authors predict that the use of the name SARS-CoV-2 might have adverse effects, both socially and economically. On these grounds, the authors suggest that the name of the new virus is changed to human coronavirus 2019 (HCoV-19). Although these concerns and suggestions are appreciated, we feel that the adoption of SARS-CoV-2 by the Coronavirus Study Group was appropriate.
Yuntao Wu; Wenzhe Ho; Yaowei Huang; Dong-Yan Jin; Shiyue Li; Shan-Lu Liu; Xuefeng Liu; Jianming Qiu; Yongming Sang; Qiuhong Wang; Kwok-Yung Yuen; Zhi-Ming Zheng. SARS-CoV-2 is an appropriate name for the new coronavirus. The Lancet 2020, 395, 949 -950.
AMA StyleYuntao Wu, Wenzhe Ho, Yaowei Huang, Dong-Yan Jin, Shiyue Li, Shan-Lu Liu, Xuefeng Liu, Jianming Qiu, Yongming Sang, Qiuhong Wang, Kwok-Yung Yuen, Zhi-Ming Zheng. SARS-CoV-2 is an appropriate name for the new coronavirus. The Lancet. 2020; 395 (10228):949-950.
Chicago/Turabian StyleYuntao Wu; Wenzhe Ho; Yaowei Huang; Dong-Yan Jin; Shiyue Li; Shan-Lu Liu; Xuefeng Liu; Jianming Qiu; Yongming Sang; Qiuhong Wang; Kwok-Yung Yuen; Zhi-Ming Zheng. 2020. "SARS-CoV-2 is an appropriate name for the new coronavirus." The Lancet 395, no. 10228: 949-950.
Currently there is no effective antiviral therapy for SARS-CoV-2 infection, which frequently leads to fatal inflammatory responses and acute lung injury. Here, we discuss the various mechanisms of SARS-CoV-mediated inflammation. We also assume that SARS-CoV-2 likely shares similar inflammatory responses. Potential therapeutic tools to reduce SARS-CoV-2-induced inflammatory responses include various methods to block FcR activation. In the absence of a proven clinical FcR blocker, the use of intravenous immunoglobulin to block FcR activation may be a viable option for the urgent treatment of pulmonary inflammation to prevent severe lung injury. Such treatment may also be combined with systemic anti-inflammatory drugs or corticosteroids. However, these strategies, as proposed here, remain to be clinically tested for effectiveness.
Yajing Fu; Yuanxiong Cheng; Yuntao Wu. Understanding SARS-CoV-2-Mediated Inflammatory Responses: From Mechanisms to Potential Therapeutic Tools. Virologica Sinica 2020, 35, 266 -271.
AMA StyleYajing Fu, Yuanxiong Cheng, Yuntao Wu. Understanding SARS-CoV-2-Mediated Inflammatory Responses: From Mechanisms to Potential Therapeutic Tools. Virologica Sinica. 2020; 35 (3):266-271.
Chicago/Turabian StyleYajing Fu; Yuanxiong Cheng; Yuntao Wu. 2020. "Understanding SARS-CoV-2-Mediated Inflammatory Responses: From Mechanisms to Potential Therapeutic Tools." Virologica Sinica 35, no. 3: 266-271.
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This article does not contain any studies with human or animal subjects performed by any of the authors. Reprints and Permissions Wu, Y. Compensation of ACE2 Function for Possible Clinical Management of 2019-nCoV-Induced Acute Lung Injury. Virol. Sin....
Yuntao Wu. Compensation of ACE2 Function for Possible Clinical Management of 2019-nCoV-Induced Acute Lung Injury. Virologica Sinica 2020, 35, 256 -258.
AMA StyleYuntao Wu. Compensation of ACE2 Function for Possible Clinical Management of 2019-nCoV-Induced Acute Lung Injury. Virologica Sinica. 2020; 35 (3):256-258.
Chicago/Turabian StyleYuntao Wu. 2020. "Compensation of ACE2 Function for Possible Clinical Management of 2019-nCoV-Induced Acute Lung Injury." Virologica Sinica 35, no. 3: 256-258.
P-selectin glycoprotein ligand-1 (PSGL-1) is a dimeric, mucin-like, 120-kDa glycoprotein that binds to P-, E-, and L-selectins. PSGL-1 is primarily expressed on the surface of lymphoid and myeloid cells and is up-regulated during inflammation to mediate leukocyte tethering and rolling on the surface of endothelium for migration into inflamed tissues. Although it has been reported that PSGL-1 expression inhibits human immunodeficiency virus type 1 (HIV-1) replication, the mechanism of PSGL-1-mediated anti-HIV activity remains to be elucidated. Here, we report that PSGL-1 in virions blocks the infectivity of HIV-1 particles by preventing the binding of particles to target cells. This inhibitory activity is independent of the viral glycoprotein present on the virus particle; the binding of particles bearing the HIV-1 envelope glycoprotein, vesicular stomatitis virus G glycoprotein, or lacking a viral glycoprotein, is impaired by PSGL-1. Mapping studies show that the extracellular, N-terminal domain of PSGL-1 is necessary for its anti-HIV-1 activity, and the PSGL-1 cytoplasmic tail contributes to its inhibition. In addition, we demonstrate that the PSGL-1-related monomeric E-selectin-binding glycoprotein CD43 also effectively blocks HIV-1 infectivity. HIV-1 infection, or the expression of either Vpu or Nef, downregulates PSGL-1 from the cell surface; the expression of Vpu appears to be primarily responsible for enabling the virus to partially escape PSGL-1-mediated restriction. Finally, we show that PSGL-1 inhibits the infectivity of other viruses such as murine leukemia virus and influenza A virus. These findings demonstrate that PSGL-1 is a broad-spectrum antiviral host factor with a novel mechanism of action.
Yajing Fu; Sijia He; Abdul Waheed; Deemah Dabbagh; Zheng Zhou; Benjamin Trinité; Zhao Wang; Jieshi Yu; Dan Wang; Feng Li; David N Levy; Hong Shang; Eric O Freed; Yuntao Wu. PSGL-1 Restricts HIV-1 Infectivity by Blocking Virus Particle Attachment to Target Cells. Proceedings 2020, 50, 77 .
AMA StyleYajing Fu, Sijia He, Abdul Waheed, Deemah Dabbagh, Zheng Zhou, Benjamin Trinité, Zhao Wang, Jieshi Yu, Dan Wang, Feng Li, David N Levy, Hong Shang, Eric O Freed, Yuntao Wu. PSGL-1 Restricts HIV-1 Infectivity by Blocking Virus Particle Attachment to Target Cells. Proceedings. 2020; 50 (1):77.
Chicago/Turabian StyleYajing Fu; Sijia He; Abdul Waheed; Deemah Dabbagh; Zheng Zhou; Benjamin Trinité; Zhao Wang; Jieshi Yu; Dan Wang; Feng Li; David N Levy; Hong Shang; Eric O Freed; Yuntao Wu. 2020. "PSGL-1 Restricts HIV-1 Infectivity by Blocking Virus Particle Attachment to Target Cells." Proceedings 50, no. 1: 77.
Human immunodeficiency virus (HIV) actively modulates the protein stability of host cells to optimize viral replication. To systematically examine this modulation in HIV infection, we used isobaric tag-based mass spectrometry to quantify changes in the abundance of over 14,000 proteins during HIV-1 infection of human primary CD4+ T cells. We identified P-selectin glycoprotein ligand 1 (PSGL-1) as an HIV-1 restriction factor downregulated by HIV-1 Vpu, which binds to PSGL-1 and induces its ubiquitination and degradation through the ubiquitin ligase SCFβ-TrCP2. PSGL-1 is induced by interferon-γ in activated CD4+ T cells to inhibit HIV-1 reverse transcription and potently block viral infectivity by incorporating in progeny virions. This infectivity block is antagonized by Vpu via PSGL-1 degradation. We further show that PSGL-1 knockdown can significantly abolish the anti-HIV activity of interferon-γ in primary CD4+ T cells. Our study identifies an HIV restriction factor and a key mediator of interferon-γ's anti-HIV activity.
Ying Liu; Yajing Fu; Qian Wang; Mushan Li; Zheng Zhou; Deemah Dabbagh; Chunyan Fu; Hang Zhang; Shuo Li; Tengjiang Zhang; Jing Gong; Xiaohui Kong; Weiwei Zhai; Jiaming Su; Jianping Sun; Yonghong Zhang; Xiao-Fang Yu; Zhen Shao; Feng Zhou; Yuntao Wu; Xu Tan. Proteomic profiling of HIV-1 infection of human CD4+ T cells identifies PSGL-1 as an HIV restriction factor. Nature Microbiology 2019, 4, 813 -825.
AMA StyleYing Liu, Yajing Fu, Qian Wang, Mushan Li, Zheng Zhou, Deemah Dabbagh, Chunyan Fu, Hang Zhang, Shuo Li, Tengjiang Zhang, Jing Gong, Xiaohui Kong, Weiwei Zhai, Jiaming Su, Jianping Sun, Yonghong Zhang, Xiao-Fang Yu, Zhen Shao, Feng Zhou, Yuntao Wu, Xu Tan. Proteomic profiling of HIV-1 infection of human CD4+ T cells identifies PSGL-1 as an HIV restriction factor. Nature Microbiology. 2019; 4 (5):813-825.
Chicago/Turabian StyleYing Liu; Yajing Fu; Qian Wang; Mushan Li; Zheng Zhou; Deemah Dabbagh; Chunyan Fu; Hang Zhang; Shuo Li; Tengjiang Zhang; Jing Gong; Xiaohui Kong; Weiwei Zhai; Jiaming Su; Jianping Sun; Yonghong Zhang; Xiao-Fang Yu; Zhen Shao; Feng Zhou; Yuntao Wu; Xu Tan. 2019. "Proteomic profiling of HIV-1 infection of human CD4+ T cells identifies PSGL-1 as an HIV restriction factor." Nature Microbiology 4, no. 5: 813-825.
A functional HIV cure requires immune reconstitution for lasting viremia control. A major immune dysfunction persisting in HIV infection is the impairment of T helper cell migration and homing to lymphoid tissues such as GALTs (gut-associated lymphoid tissues). ART (antiretroviral therapy) does not fully restore T cell motility for tissue repopulation. The molecular mechanism dictating this persistent T cell dysfunction is not understood. Cofilin is an actin-depolymerizing factor that regulates actin dynamics for T cell migration. Here, we demonstrate that blood CD4 T cells from HIV-infected patients (n = 193), with or without ART, exhibit significantly lower levels of cofilin phosphorylation (hyperactivation) than those from healthy controls (n = 100; ratio, 1.1:2.3; P < 0.001); cofilin hyperactivation is also associated with poor CD4 T cell recovery following ART. These results suggest an HIV-mediated systemic dysregulation of T cell motility that cannot be repaired solely by ART. We further demonstrate that stimulating blood CD4 T cells with an anti–human α4β7 integrin antibody can trigger signal transduction and modulate the cofilin pathway, partially restoring T cell motility in vitro. However, we also observed that severe T cell motility defect caused by high degrees of cofilin hyperactivation was not repairable by the anti-integrin antibody, demonstrating a mechanistic hindrance to restore immune functions in vivo. Our study suggests that cofilin is a key molecule that may need to be therapeutically targeted early for T cell tissue repopulation, immune reconstitution, and immune control of viremia.
Sijia He; Yajing Fu; Jia Guo; Mark Spear; Jiuling Yang; Benjamin Trinité; Chaolong Qin; Shuai Fu; Yongjun Jiang; Zining Zhang; Junjie Xu; Haibo Ding; David N. Levy; Wanjun Chen; Emanuel Petricoin; Lance A. Liotta; Hong Shang; Yuntao Wu. Cofilin hyperactivation in HIV infection and targeting the cofilin pathway using an anti-α4β7 integrin antibody. Science Advances 2019, 5, eaat7911 .
AMA StyleSijia He, Yajing Fu, Jia Guo, Mark Spear, Jiuling Yang, Benjamin Trinité, Chaolong Qin, Shuai Fu, Yongjun Jiang, Zining Zhang, Junjie Xu, Haibo Ding, David N. Levy, Wanjun Chen, Emanuel Petricoin, Lance A. Liotta, Hong Shang, Yuntao Wu. Cofilin hyperactivation in HIV infection and targeting the cofilin pathway using an anti-α4β7 integrin antibody. Science Advances. 2019; 5 (1):eaat7911.
Chicago/Turabian StyleSijia He; Yajing Fu; Jia Guo; Mark Spear; Jiuling Yang; Benjamin Trinité; Chaolong Qin; Shuai Fu; Yongjun Jiang; Zining Zhang; Junjie Xu; Haibo Ding; David N. Levy; Wanjun Chen; Emanuel Petricoin; Lance A. Liotta; Hong Shang; Yuntao Wu. 2019. "Cofilin hyperactivation in HIV infection and targeting the cofilin pathway using an anti-α4β7 integrin antibody." Science Advances 5, no. 1: eaat7911.
Recently, some generative adversarial network (GAN)-based super-resolution (SR) methods have progressed to the point where they can produce photo-realistic natural images by using a generator (G) and discriminator (D) adversarial scheme. However, vanilla GAN-based SR methods cannot achieve good reconstruction and perceptual fidelity on real-world facial images at the same time. Because of D loss, them are hard to converge stably, which may cause the model collapse. In this paper, we present an Enhanced Discriminative Generative Adversarial Network (EDGAN) for SR facial recognition to achieve better reconstruction and perceptual fidelities. First, we discover that a versatile D boosts the adversarial framework to a preferable Nash equilibrium. Then, we design the D via dense connections, which brings more stable adversarial loss. Furthermore, a novel perceptual loss function, by reusing the intermediate features of D, is used to eliminate the gradient vanishing problem of Gs. To our knowledge, this is the first framework to focus on improving the performance of the D. Quantitatively, experimental results show the advantages of EDGAN on two widely used facial image databases against the state-of-the-art methods with different terms. EDGAN performs sharper and realistic results on real-world facial images with large pose and illumination variations than its competitors.
Xi Yang; Tao Lu; Jiaming Wang; Yanduo Zhang; Yuntao Wu; Zhongyuan Wang; Zixiang Xiong. Enhanced Discriminative Generative Adversarial Network for Face Super-Resolution. Transactions on Petri Nets and Other Models of Concurrency XV 2018, 441 -452.
AMA StyleXi Yang, Tao Lu, Jiaming Wang, Yanduo Zhang, Yuntao Wu, Zhongyuan Wang, Zixiang Xiong. Enhanced Discriminative Generative Adversarial Network for Face Super-Resolution. Transactions on Petri Nets and Other Models of Concurrency XV. 2018; ():441-452.
Chicago/Turabian StyleXi Yang; Tao Lu; Jiaming Wang; Yanduo Zhang; Yuntao Wu; Zhongyuan Wang; Zixiang Xiong. 2018. "Enhanced Discriminative Generative Adversarial Network for Face Super-Resolution." Transactions on Petri Nets and Other Models of Concurrency XV , no. : 441-452.
Yingxin Ma; Zhike He; Tianwei Tan; Wei Li; Zhiping Zhang; Shuang Song; Xiaowei Zhang; Qinxue Hu; Peng Zhou; Yuntao Wu; Xian-En Zhan; Zongqiang Cui. Real-time imaging of single HIV-1 disassembly with multicolor viral particles. Nanomedicine: Nanotechnology, Biology and Medicine 2018, 14, 1873 .
AMA StyleYingxin Ma, Zhike He, Tianwei Tan, Wei Li, Zhiping Zhang, Shuang Song, Xiaowei Zhang, Qinxue Hu, Peng Zhou, Yuntao Wu, Xian-En Zhan, Zongqiang Cui. Real-time imaging of single HIV-1 disassembly with multicolor viral particles. Nanomedicine: Nanotechnology, Biology and Medicine. 2018; 14 (5):1873.
Chicago/Turabian StyleYingxin Ma; Zhike He; Tianwei Tan; Wei Li; Zhiping Zhang; Shuang Song; Xiaowei Zhang; Qinxue Hu; Peng Zhou; Yuntao Wu; Xian-En Zhan; Zongqiang Cui. 2018. "Real-time imaging of single HIV-1 disassembly with multicolor viral particles." Nanomedicine: Nanotechnology, Biology and Medicine 14, no. 5: 1873.
In HIV infected macrophages, a large population of viral genomes persists as the unintegrated form (uDNA) that is transcriptionally active. However, how this transcriptional activity is controlled remains unclear. In this report, we investigated whether Tat, the viral transactivator of transcription, is involved in uDNA transcription. We demonstrate that de novo Tat activity is generated from uDNA, and this uDNA-derived Tat (uTat) transactivates the uDNA LTR. In addition, uTat is required for the transcriptional persistence of uDNA that is assembled into repressive episomal minichromatin. In the absence of uTat, uDNA minichromatin is gradually silenced, but remains highly inducible by HDAC inhibitors (HDACi). Therefore, functionally, uTat antagonizes uDNA minichromatin repression to maintain persistent viral transcription in macrophages. uTat-mediated viral persistence may establish a viral reservoir in macrophages where uDNA were found to persist.
Beatrix Meltzer; Deemah Dabbagh; Jia Guo; Fatah Kashanchi; Mudit Tyagi; Yuntao Wu. Tat controls transcriptional persistence of unintegrated HIV genome in primary human macrophages. Virology 2018, 518, 241 -252.
AMA StyleBeatrix Meltzer, Deemah Dabbagh, Jia Guo, Fatah Kashanchi, Mudit Tyagi, Yuntao Wu. Tat controls transcriptional persistence of unintegrated HIV genome in primary human macrophages. Virology. 2018; 518 ():241-252.
Chicago/Turabian StyleBeatrix Meltzer; Deemah Dabbagh; Jia Guo; Fatah Kashanchi; Mudit Tyagi; Yuntao Wu. 2018. "Tat controls transcriptional persistence of unintegrated HIV genome in primary human macrophages." Virology 518, no. : 241-252.
Yuntao Wu. Actin. Encyclopedia of AIDS 2018, 6 -13.
AMA StyleYuntao Wu. Actin. Encyclopedia of AIDS. 2018; ():6-13.
Chicago/Turabian StyleYuntao Wu. 2018. "Actin." Encyclopedia of AIDS , no. : 6-13.
Yuntao Wu. Cofilin, Trafficking. Encyclopedia of AIDS 2018, 332 -336.
AMA StyleYuntao Wu. Cofilin, Trafficking. Encyclopedia of AIDS. 2018; ():332-336.
Chicago/Turabian StyleYuntao Wu. 2018. "Cofilin, Trafficking." Encyclopedia of AIDS , no. : 332-336.
Jia Guo; Yuntao Wu. Genistein and HIV Infection. HIV/AIDS 2018, 125 -134.
AMA StyleJia Guo, Yuntao Wu. Genistein and HIV Infection. HIV/AIDS. 2018; ():125-134.
Chicago/Turabian StyleJia Guo; Yuntao Wu. 2018. "Genistein and HIV Infection." HIV/AIDS , no. : 125-134.