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Thymic Epithelial Cell Reprogramming And Co-Culture With T-Cell Progenitors, Isabelle Riddle 2018 University of Georgia

Thymic Epithelial Cell Reprogramming And Co-Culture With T-Cell Progenitors, Isabelle Riddle

Georgia Undergraduate Research Conference (GURC)

The thymus is a lymphoid organ found in the neck region of vertebrates that produces T-cells critical for the adaptive immune system. However, thymus involution relatively early in the aging process leads to a deterioration in immune function. Models in regenerative medicine have the prospect of replacing lost cells and combating the problem. This experiment is a preliminary step geared towards achieving the overarching goal of boosting long-term maintenance of adaptive immunity over the typical aging process or following therapeutic immune depletion. Specifically, the objective is to show that disparate cell lineages can be reprogrammed—both morphologically and physiologically—using ...


Microrna-96 Promotes Schistosomiasis Hepatic Fibrosis In Mice By Suppressing Smad7, Xufeng Luo, Dongmei Zhang, Jun Xie, Qin Su, Xing He, Ruipu Bai, Guangping Gao, Weiqing Pan 2018 Second Military Medical University

Microrna-96 Promotes Schistosomiasis Hepatic Fibrosis In Mice By Suppressing Smad7, Xufeng Luo, Dongmei Zhang, Jun Xie, Qin Su, Xing He, Ruipu Bai, Guangping Gao, Weiqing Pan

UMass Center for Clinical and Translational Science Supported Publications

Infection with Schistosoma causes aberrant expression of host microRNAs (miRNAs), and normalizing the levels of dysregulated miRNAs can attenuate pathology. Here, we show that the host miRNA, miR-96, is markedly upregulated during the progression of hepatic schistosomiasis. We demonstrate that elevation of miR-96 induces hepatic fibrosis in infected mice by suppressing the expression of its target gene, Smad7. We show that infection with Schistosoma induces the expression of transforming growth factor beta1 (TGF-beta1), which in turn upregulates the expression of miR-96 through SMAD2/3-DROSHA-mediated post-transcriptional regulation. Furthermore, inhibition of miR-96 with recombinant adeno-associated virus 8 (rAAV8)-mediated delivery of Tough ...


Protection Induced By A Francisella Tularensis Subunit Vaccine Delivered By Glucan Particles, Adam O. Whelan, Helen C. Flick-Smith, Jane Homan, Zu T. Shen, Zoe Carpenter, Payam Khoshkenar, Ambily Abraham, Nicola J. Walker, Stuart M. Levitz, Gary R. Ostroff, Petra C. F. Oyston 2018 Dstl Porton Down

Protection Induced By A Francisella Tularensis Subunit Vaccine Delivered By Glucan Particles, Adam O. Whelan, Helen C. Flick-Smith, Jane Homan, Zu T. Shen, Zoe Carpenter, Payam Khoshkenar, Ambily Abraham, Nicola J. Walker, Stuart M. Levitz, Gary R. Ostroff, Petra C. F. Oyston

Open Access Articles

Francisella tularensis is an intracellular pathogen causing the disease tularemia, and an organism of concern to biodefence. There is no licensed vaccine available. Subunit approaches have failed to induce protection, which requires both humoral and cellular immune memory responses, and have been hampered by a lack of understanding as to which antigens are immunoprotective. We undertook a preliminary in silico analysis to identify candidate protein antigens. These antigens were then recombinantly expressed and encapsulated into glucan particles (GPs), purified Saccharomyces cerevisiae cell walls composed primarily of beta-1,3-glucans. Immunological profiling in the mouse was used to down-selection to seven lead ...


Adeno-Associated Virus Neutralizing Antibodies In Large Animals And Their Impact On Brain Intraparenchymal Gene Transfer, Dan Wang, Li Zhong, Mengxin Li, Jia Li, Karen Tran, Lingzhi Ren, Ran He, Jun Xie, Richard P. Moser, Cara Fraser, Tim Kuchel, Miguel Sena-Esteves, Terence R. Flotte, Neil Aronin, Guangping Gao 2018 University of Massachusetts Medical School

Adeno-Associated Virus Neutralizing Antibodies In Large Animals And Their Impact On Brain Intraparenchymal Gene Transfer, Dan Wang, Li Zhong, Mengxin Li, Jia Li, Karen Tran, Lingzhi Ren, Ran He, Jun Xie, Richard P. Moser, Cara Fraser, Tim Kuchel, Miguel Sena-Esteves, Terence R. Flotte, Neil Aronin, Guangping Gao

Open Access Articles

Pre-existing neutralizing antibody (NAb) against adeno-associated virus (AAV) commonly found in primates is a major host barrier that can severely compromise in vivo gene transfer by AAV vectors. To achieve proof-of-concept success in clinical development of recombinant AAV (rAAV)-based in vivo gene therapy, it is crucial to consider the potential interference of NAb and to enroll serologically compatible study subjects. In this study, we report a large AAV NAb dataset comprising multiple large animal species and AAV serotypes and compare two NAb assays based on in vitro or in vivo transduction inhibition, respectively. Together with previously published AAV seroepidemiology ...


T Cell Epitope Engineering: An Avian H7n9 Influenza Vaccine Strategy For Pandemic Preparedness And Response, Leonard Moise, Bethany M. Biron, Christine M. Boyle, Nese Kurt Yilmaz, Hyesun Jang, Celia A. Schiffer, Ted M. Ross, William D. Martin, Anne S. De Groot 2018 University of Rhode Island

T Cell Epitope Engineering: An Avian H7n9 Influenza Vaccine Strategy For Pandemic Preparedness And Response, Leonard Moise, Bethany M. Biron, Christine M. Boyle, Nese Kurt Yilmaz, Hyesun Jang, Celia A. Schiffer, Ted M. Ross, William D. Martin, Anne S. De Groot

Schiffer Lab Publications

The delayed availability of vaccine during the 2009 H1N1 influenza pandemic created a sense of urgency to better prepare for the next influenza pandemic. Advancements in manufacturing technology, speed and capacity have been achieved but vaccine effectiveness remains a significant challenge. Here, we describe a novel vaccine design strategy called immune engineering in the context of H7N9 influenza vaccine development. The approach combines immunoinformatic and structure modeling methods to promote protective antibody responses against H7N9 hemagglutinin (HA) by engineering whole antigens to carry seasonal influenza HA memory CD4(+) T cell epitopes - without perturbing native antigen structure - by galvanizing HA-specific memory ...


One Group's Historical Reflections On Dna Vaccine Development, Ellen F. Fynan, Shan Lu, Harriet L. Robinson 2018 Worcester State College

One Group's Historical Reflections On Dna Vaccine Development, Ellen F. Fynan, Shan Lu, Harriet L. Robinson

Open Access Articles

DNA vaccines were pioneered by several groups in the early 1990s. This article presents the reflections of one of these groups on their work with retroviral vectors in chickens that contributed to the discovery and early development of DNA vaccines. Although the findings were initially met with skepticism, the work presented here combined with that of others founded a new method of vaccination: the direct inoculation of purified DNA encoding the target antigen.


Identification And Characterization Of Human Monoclonal Antibodies For Immunoprophylaxis Against Enterotoxigenic Escherichia Coli Infection, Serena Giuntini, Matteo Stoppato, Maja Sedic, Ejemel Monir, Jessica R. Pondish, Danielle Wisheart, Zachary Schiller, William D. Thomas Jr., Eileen M. Barry, Lisa Cavacini, mark S. klempner, Yan Wang 2018 University of Massachusetts Medical School

Identification And Characterization Of Human Monoclonal Antibodies For Immunoprophylaxis Against Enterotoxigenic Escherichia Coli Infection, Serena Giuntini, Matteo Stoppato, Maja Sedic, Ejemel Monir, Jessica R. Pondish, Danielle Wisheart, Zachary Schiller, William D. Thomas Jr., Eileen M. Barry, Lisa Cavacini, Mark S. Klempner, Yan Wang

Open Access Articles

Background. Enterotoxigenic Escherichia coli (ETEC) cause diarrheal illness in infants in the developing world and travelers to endemic countries including military personnel. ETEC infection of the host involves colonization of the small intestinal epithelium and toxin secretion leading to watery diarrhea. There is currently no vaccine licensed to prevent ETEC. CFA/I is one of the most common colonization factor antigens (CFAs). The CFA/I adhesin subunit, CfaE, is required for ETEC adhesion to host intestinal cells. Human antibodies against CfaE have potential to block colonization of ETEC and serve as an immunoprophylactic against ETEC-related diarrhea.

Methods. Mice transgenic for ...


Quantitative Profiling Of The Lymph Node Clearance Capacity, Cristina C. Clement, Wei Wang, Monika Dzieciatkowska, Marco Cortese, Kirk C. Hansen, Aniuska Becerra, Sangeetha Thangaswamy, Irina Nizamutdinova, Jee-Young Moon, Lawrence J. Stern, Anatoliy A. Gashev, David Zawieja, Laura Santambrogio 2018 Albert Einstein College of Medicine

Quantitative Profiling Of The Lymph Node Clearance Capacity, Cristina C. Clement, Wei Wang, Monika Dzieciatkowska, Marco Cortese, Kirk C. Hansen, Aniuska Becerra, Sangeetha Thangaswamy, Irina Nizamutdinova, Jee-Young Moon, Lawrence J. Stern, Anatoliy A. Gashev, David Zawieja, Laura Santambrogio

Open Access Articles

Transport of tissue-derived lymphatic fluid and clearance by draining lymph nodes are pivotal for maintenance of fluid homeostasis in the body and for immune-surveillance of the self- and non-self-proteomes. Yet a quantitative analysis of nodal filtration of the tissue-derived proteome present in lymphatic fluid has not been reported. Here we quantified the efficiency of nodal clearance of the composite proteomic load using label-free and isotope-labeling proteomic analysis of pre-nodal and post-nodal samples collected by direct cannulation. These results were extended by quantitation of the filtration efficiency of fluorophore-labeled proteins, bacteria, and beads infused at physiological flow rates into pre-nodal lymphatic ...


Total Body Cd4+ T Cell Dynamics In Treated And Untreated Siv Infection Revealed By In Vivo Imaging, Michele Di Mascio, Sharat Srinivasula, Insook Kim, Gorka Duralde, Alexis St. Claire, Paula DeGrange, Marisa St. Claire, Keith A. Reimann, Erin E. Gabriel, Jorge Carrasquillo, Richard C. Reba, Chang Paik, Henry C. Lane 2018 National Institute of Allergy and Infectious Diseases

Total Body Cd4+ T Cell Dynamics In Treated And Untreated Siv Infection Revealed By In Vivo Imaging, Michele Di Mascio, Sharat Srinivasula, Insook Kim, Gorka Duralde, Alexis St. Claire, Paula Degrange, Marisa St. Claire, Keith A. Reimann, Erin E. Gabriel, Jorge Carrasquillo, Richard C. Reba, Chang Paik, Henry C. Lane

Open Access Articles

The peripheral blood represents only a small fraction of the total number of lymphocytes in the body. To develop a more thorough understanding of T cell dynamics, including the effects of SIV/SHIV/HIV infection on immune cell depletion and immune reconstitution following combination antiretroviral therapy (cART), one needs to utilize approaches that allow direct visualization of lymphoid tissues. In the present study, noninvasive in vivo imaging of the CD4+ T cell pool has revealed that the timing of the CD4+ T cell pool reconstitution following initiation of ART in SIV-infected nonhuman primates (NHPs) appears seemingly stochastic among clusters of ...


Maximising The Global Health Impact Of Future Hiv Cure-Related Interventions Through Advance Planning, Regina Brown, Steven G. Deeks, Nir Eyal 2018 University of Massachusetts Medical School

Maximising The Global Health Impact Of Future Hiv Cure-Related Interventions Through Advance Planning, Regina Brown, Steven G. Deeks, Nir Eyal

Open Access Articles

Thinking about public health impact should inform HIV curative investigations. Should an effective HIV cure or sustained viral remission intervention emerge from ongoing investigations, implementation strategies aimed at ensuring global access will be needed if these approaches are to be impactful, and planning accordingly makes sense now. Specifically, we discuss three key access barriers to future cure-related interventions: high cost of the strategy; non-financial challenges to procurement, distribution and point-of-care delivery; and non-adherence and the need for long-term monitoring. As we argue, plans and decision-making for overcoming each of these barriers will need to be developed in advance. An evaluation ...


Pd-L1 Is Expressed On Human Platelets And Is Affected By Immune Checkpoint Therapy, Verena Rolfes, Christian Idel, Ralph Pries, Kirstin Plotze-Martin, Jens Habermann, Timo Gemoll, Sabine Bohnet, Eicke Latz, Julika Ribbat-Idel, Bernardo S. Franklin, Barbara Wollenberg 2018 University of Bonn

Pd-L1 Is Expressed On Human Platelets And Is Affected By Immune Checkpoint Therapy, Verena Rolfes, Christian Idel, Ralph Pries, Kirstin Plotze-Martin, Jens Habermann, Timo Gemoll, Sabine Bohnet, Eicke Latz, Julika Ribbat-Idel, Bernardo S. Franklin, Barbara Wollenberg

Open Access Articles

Cancer immunotherapy has been revolutionised by drugs that enhance the ability of the immune system to detect and fight tumors. Immune checkpoint therapies that target the programmed death-1 receptor (PD-1), or its ligand (PD-L1) have shown unprecedented rates of durable clinical responses in patients with various cancer types. However, there is still a large fraction of patients that do not respond to checkpoint inhibitors, and the challenge remains to find cellular and molecular cues that could predict which patients would benefit from these therapies. Using a series of qualitative and quantitative methods we show here that PBMCs and platelets from ...


Immunohistochemical Expression And Prognostic Value Of Pd-L1 In Extrapulmonary Small Cell Carcinoma: A Single Institution Experience, Mohammed Salhab, Yazan Migdady, Melanie Donahue, Yiqin Xiong, Karen A. Dresser, William Walsh, Benjamin J. Chen, James Liebmann 2018 University of Massachusetts Medical School

Immunohistochemical Expression And Prognostic Value Of Pd-L1 In Extrapulmonary Small Cell Carcinoma: A Single Institution Experience, Mohammed Salhab, Yazan Migdady, Melanie Donahue, Yiqin Xiong, Karen A. Dresser, William Walsh, Benjamin J. Chen, James Liebmann

Open Access Articles

BACKGROUND: Extrapulmonary small cell carcinomas (ESCC) are rare but aggressive tumors. Relapses are common despite treatment with chemotherapy and/or radiotherapy. Prospective data for treatment of ESCC are lacking; treatment of these cancers usually incorporates lung small cell carcinoma treatment recommendations. Cancer staging remains the most important prognostic factor. Cancer immunotherapy targeting the PD-1/PD-L1 pathway has shown efficacy in multiple tumor types, and could be an appealing treatment strategy for these rare tumors.

METHODS: We investigated PD-L1 expression by immunochemistry (IHC) in ESCCs diagnosed at University of Massachusetts Medical Center, from 1999 to 2016. 34 cases with sufficient material ...


Efficacy Of A Respiratory Syncytial Virus Vaccine Candidate In A Maternal Immunization Model, Jorge C. G. Blanco, Lioubov M. Pletneva, Lori McGinnes Cullen, Raymonde O. Otoa, Mira C. Patel, Lurds R. Fernando, Marina S. Boukhvalova, Trudy G. Morrison 2018 Sigmovir Biosystems Inc.

Efficacy Of A Respiratory Syncytial Virus Vaccine Candidate In A Maternal Immunization Model, Jorge C. G. Blanco, Lioubov M. Pletneva, Lori Mcginnes Cullen, Raymonde O. Otoa, Mira C. Patel, Lurds R. Fernando, Marina S. Boukhvalova, Trudy G. Morrison

Open Access Articles

Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in infants. Maternal immunization is an option to increase maternal antibody levels and protect infants from infection. Here we assess the efficacy of virus-like particle (VLP) vaccine candidates containing stabilized pre-fusion (pre-F) or post-fusion (post-F) conformations of the RSV F protein and the attachment RSV G protein in a maternal immunization model using cotton rats. VLP vaccines containing RSV F and G proteins strongly boost pre-existing RSV immunity in dams preventing their perinatal drop in immunity. Boosting is stronger for the pre-F VLP than for the post-F VLP or ...


A Novel Sialylation Site On Neisseria Gonorrhoeae Lipooligosaccharide Links Heptose Ii Lactose Expression With Pathogenicity, Sanjay Ram, Sunita Gulati, Lisa A. Lewis, Srinjoy Chakraborti, Bo Zheng, Rosane B. de Oliveira, George W. Reed, Andrew D. Cox, Jianjun Li, Frank St. Michael, Jacek Stupak, Xiao-Hong Su, Sudeshna Saha, Corinna S. Landig, Ajit Varki, Peter A. Rice 2018 University of Massachusetts Medical School

A Novel Sialylation Site On Neisseria Gonorrhoeae Lipooligosaccharide Links Heptose Ii Lactose Expression With Pathogenicity, Sanjay Ram, Sunita Gulati, Lisa A. Lewis, Srinjoy Chakraborti, Bo Zheng, Rosane B. De Oliveira, George W. Reed, Andrew D. Cox, Jianjun Li, Frank St. Michael, Jacek Stupak, Xiao-Hong Su, Sudeshna Saha, Corinna S. Landig, Ajit Varki, Peter A. Rice

University of Massachusetts Medical School Faculty Publications

Sialylation of lacto-N-neotetraose (LNnT) extending from heptose I (HepI) of gonococcal lipooligosaccharide (LOS) contributes to pathogenesis. Previously, gonococcal LOS sialyltransterase (Lst) was shown to sialylate LOS in Triton X-100 extracts of strain 15253, which expresses lactose from both HepI and HepII, the minimal structure required for mAb 2C7 binding. Ongoing work has shown that growth of 15253 in cytidine monophospho-N-acetylneuraminic acid (CMP-Neu5Ac)-containing media enables binding to CD33/Siglec-3, a cell surface receptor that binds sialic acid, suggesting that lactose termini on LOS of intact gonococci can be sialylated. Neu5Ac was detected on LOSs of strains 15253 and a MS11 ...


Intron-Containing Rna From The Hiv-1 Provirus Activates Type I Interferon And Inflammatory Cytokines, Sean M. McCauley, Kyusik Kim, Anetta Nowosielska, Ann Dauphin, Leonid Yurkovetskiy, William E. Diehl, Jeremy Luban 2018 University of Massachusetts Medical School

Intron-Containing Rna From The Hiv-1 Provirus Activates Type I Interferon And Inflammatory Cytokines, Sean M. Mccauley, Kyusik Kim, Anetta Nowosielska, Ann Dauphin, Leonid Yurkovetskiy, William E. Diehl, Jeremy Luban

Program in Molecular Medicine Publications and Presentations

HIV-1-infected people who take drugs that suppress viremia to undetectable levels are protected from developing AIDS. Nonetheless, these individuals have chronic inflammation associated with heightened risk of cardiovascular pathology. HIV-1 establishes proviruses in long-lived CD4+ memory T cells, and perhaps other cell types, that preclude elimination of the virus even after years of continuous antiviral therapy. Though the majority of proviruses that persist during antiviral therapy are defective for production of infectious virions, many are expressed, raising the possibility that the HIV-1 provirus or its transcripts contribute to ongoing inflammation. Here we found that the HIV-1 provirus activated innate immune ...


Tumor Surveillance Using Liquid Biome In Pediatric High Grade Gliomas, Erin Bonner, Eshini Panditharatna, Madhuri Kambhampati, Stefaan Van Gool, Wilfried Stuecker, Roger J. Packer, Javad Nazarian 2018 Children's National Health System

Tumor Surveillance Using Liquid Biome In Pediatric High Grade Gliomas, Erin Bonner, Eshini Panditharatna, Madhuri Kambhampati, Stefaan Van Gool, Wilfried Stuecker, Roger J. Packer, Javad Nazarian

GW Research Days 2016 - Present

Immunotherapy is currently being used to treat pediatric brain cancer, though its efficacy in treating patients with diffuse intrinsic pontine glioma (DIPG), the deadliest pediatric brain tumor, has not been evaluated. MRI is the gold standard for monitoring tumor response to therapy, but is limited by pseudoresponse and psuedoprogression: post-treatment, immune cells infiltrate the primary tumor causing transient tumor enlargement, which falsely resembles tumor progression on MRI. Thus, it is critical to develop more accurate approaches to monitor tumor response to immunotherapy. Here, we use a liquid biopsy platform we have already established to monitor tumor response to therapy, to ...


New Vaccine Formulations Containing A Modified Version Of The Amastigote 2 Antigen And The Non-Virulent Trypanosoma Cruzi Cl-14 Strain Are Highly Antigenic And Protective Against Leishmania Infantum Challenge, Ana Paula M. M. Almeida, Leopoldo F.M. Machado, Daniel Doro, Frederico C. Nascimento, Leonardo Damasceno, Ricardo T. Gazzinelli, Ana Paula Fernandes, Caroline Junqueira 2018 Federal University of Minas Gerais

New Vaccine Formulations Containing A Modified Version Of The Amastigote 2 Antigen And The Non-Virulent Trypanosoma Cruzi Cl-14 Strain Are Highly Antigenic And Protective Against Leishmania Infantum Challenge, Ana Paula M. M. Almeida, Leopoldo F.M. Machado, Daniel Doro, Frederico C. Nascimento, Leonardo Damasceno, Ricardo T. Gazzinelli, Ana Paula Fernandes, Caroline Junqueira

Open Access Articles

Visceral leishmaniasis (VL) is a major public health issue reported as the second illness in mortality among all tropical diseases. Clinical trials have shown that protection against VL is associated with robust T cell responses, especially those producing IFN-gamma. The Leishmania amastigote 2 (A2) protein has been repeatedly described as immunogenic and protective against VL in different animal models; it is recognized by human T cells, and it is also commercially available in a vaccine formulation containing saponin against canine VL. Moving toward a more appropriate formulation for human vaccination, here, we tested a new optimized version of the recombinant ...


Humanized Mice In Studying Efficacy And Mechanisms Of Pd-1-Targeted Cancer Immunotherapy, Minan Wang, Michael A. Brehm, Dale L. Greiner 2018 The Jackson Laboratory

Humanized Mice In Studying Efficacy And Mechanisms Of Pd-1-Targeted Cancer Immunotherapy, Minan Wang, Michael A. Brehm, Dale L. Greiner

Open Access Articles

Establishment of an in vivo small animal model of human tumor and human immune system interaction would enable preclinical investigations into the mechanisms underlying cancer immunotherapy. To this end, nonobese diabetic (NOD).Cg- Prkdc(scid)IL2rg(tm1Wjl)/Sz (null; NSG) mice were transplanted with human (h)CD34(+) hematopoietic progenitor and stem cells, which leads to the development of human hematopoietic and immune systems [humanized NSG (HuNSG)]. HuNSG mice received human leukocyte antigen partially matched tumor implants from patient-derived xenografts [PDX; non-small cell lung cancer (NSCLC), sarcoma, bladder cancer, and triple-negative breast cancer (TNBC)] or from a TNBC cell line-derived xenograft ...


Use Of Elispot Assay To Study Hbs-Specific B Cell Responses In Vaccinated And Hbv Infected Humans, Chen Tian, Yuxin Chen, Yong Liu, Shixia Wang, Yang Li, Guiyang Wang, Juan Xia, Xiang-An Zhao, Rui Huang, Shan Lu, Chao Wu 2018 Nanjing University

Use Of Elispot Assay To Study Hbs-Specific B Cell Responses In Vaccinated And Hbv Infected Humans, Chen Tian, Yuxin Chen, Yong Liu, Shixia Wang, Yang Li, Guiyang Wang, Juan Xia, Xiang-An Zhao, Rui Huang, Shan Lu, Chao Wu

Open Access Articles

Hepatitis B surface antibody (HBsAb) plays a critical role in protecting against infection of hepatitis B virus (HBV) and were extensively studied in literature. At the same time, the status of hepatitis B surface antigen (HBs)-specific B cells in both vaccinated and HBV infected people received limited attention. In the current study, we adopted a highly specific B-cell Enzyme Linked ImmunoSpot (ELISpot) assay to analyze HBs-specific B cells in various clinical settings: healthy individuals with the history of HBV vaccination before and after receiving an extra HBV vaccine boost, people chronically infected with HBV (CHB) in various clinical stages ...


Hiv-1 R5 Macrophage-Tropic Envelope Glycoprotein Trimers Bind Cd4 With High Affinity, While The Cd4 Binding Site On Non-Macrophage-Tropic, T-Tropic R5 Envelopes Is Occluded, Briana Quitadamo, Paul J. Peters, Alexander Repik, Olivia O'Connell, Zhongming Mou, Matthew Koch, Mohan Somasundaran, Robin M. Brody, Katherine Luzuriaga, Aaron Wallace, Shixia Wang, Shan Lu, Sean M. McCauley, Jeremy Luban, Maria J. Duenas-Decamp, Maria Paz Paz Gonzalez-Perez, Paul R. Clapham 2018 University of Massachusetts Medical School

Hiv-1 R5 Macrophage-Tropic Envelope Glycoprotein Trimers Bind Cd4 With High Affinity, While The Cd4 Binding Site On Non-Macrophage-Tropic, T-Tropic R5 Envelopes Is Occluded, Briana Quitadamo, Paul J. Peters, Alexander Repik, Olivia O'Connell, Zhongming Mou, Matthew Koch, Mohan Somasundaran, Robin M. Brody, Katherine Luzuriaga, Aaron Wallace, Shixia Wang, Shan Lu, Sean M. Mccauley, Jeremy Luban, Maria J. Duenas-Decamp, Maria Paz Paz Gonzalez-Perez, Paul R. Clapham

Program in Molecular Medicine Publications and Presentations

HIV-1 R5 variants exploit CCR5 as a coreceptor to infect both T cells and macrophages. R5 viruses that are transmitted or derived from immune tissue and peripheral blood are mainly inefficient at mediating infection of macrophages. In contrast, highly macrophage-tropic (mac-tropic) R5 viruses predominate in brain tissue and can be detected in cerebrospinal fluid but are infrequent in immune tissue or blood even in late disease. These mac-tropic R5 variants carry envelope glycoproteins (Envs) adapted to exploit low levels of CD4 on macrophages to induce infection. However, it is unclear whether this adaptation is conferred by an increased affinity of ...


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