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https://www.readbyqxmd.com/read/29773829/sequential-immunizations-with-a-panel-of-hiv-1-env-virus-like-particles-coach-immune-system-to-make-broadly-neutralizing-antibodies
#1
Teena Mohan, Zachary Berman, Sang-Moo Kang, Bao-Zhong Wang
Broadly neutralizing antibodies (bnAbs) are correlated with passive HIV/SHIV protection and are desirable components of a HIV protective immunity. In the current study, we have designed a sequential-immunization strategy with a panel of envelope glycoprotein (Env)-enriched virus-like particles (VLPs) from various HIV-1 clades (A-E) to elicit bnAbs with high breadth and potency of neutralization in rabbits. We have compared this regimen with repetitive immunizations of individual Env (subtype B) VLPs or a mixture of various Env VLPs...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29772651/properties-and-functions-of-feline-immunodeficiency-virus-gag-domains-in-virion-assembly-and-budding
#2
REVIEW
Silvia A González, José L Affranchino
Feline immunodeficiency virus (FIV) is an important cat pathogen worldwide whose biological and pathophysiological properties resemble those of human immunodeficiency virus type 1 (HIV-1). Therefore, the study of FIV not only benefits its natural host but is also useful for the development of antiviral strategies directed against HIV-1 infections in humans. FIV assembly results from the multimerization of a single but complex viral polypeptide, the Gag precursor. In this review, we will first give an overview of the current knowledge of the proteins encoded by the FIV pol , env , rev , vif, and orf-A genes, and then we will describe and discuss in detail the critical roles that each of the FIV Gag domains plays in virion morphogenesis...
May 16, 2018: Viruses
https://www.readbyqxmd.com/read/29769533/structure-of-a-cleavage-independent-hiv-env-recapitulates-the-glycoprotein-architecture-of-the-native-cleaved-trimer
#3
Anita Sarkar, Shridhar Bale, Anna-Janina Behrens, Sonu Kumar, Shailendra Kumar Sharma, Natalia de Val, Jesper Pallesen, Adriana Irimia, Devan C Diwanji, Robyn L Stanfield, Andrew B Ward, Max Crispin, Richard T Wyatt, Ian A Wilson
Furin cleavage of the HIV envelope glycoprotein is an essential step for cell entry that enables formation of well-folded, native-like glycosylated trimers, releases constraints on the fusion peptide, and limits enzymatic processing of the N-glycan shield. Here, we show that a cleavage-independent, stabilized, soluble Env trimer mimic (BG505 NFL.664) exhibits a "closed-form", native-like, prefusion conformation akin to furin-cleaved Env trimers. The crystal structure of BG505 NFL.664 at 3.39 Å resolution with two potent bNAbs also identifies the full epitopes of PGV19 and PGT122 that target the receptor binding site and N332 supersite, respectively...
May 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29767965/bifunctional-chimera-that-coordinately-targets-human-immunodeficiency-virus-1-hiv-1-envelope-gp120-and-host-cell-ccr5-co-receptor-at-the-virus-cell-interface
#4
Adel A Rashad, Li-Rui Song, Andrew P Holmes, Kriti Acharya, Shiyu Zhang, Zhi-Long Wang, Ebony Gary, Xin Xie, Vanessa Pirrone, Michele A Kutzler, Ya-Qiu Long, Irwin Chaiken
To address the urgent need for new agents to reduce the global occurrence and spread of AIDS, we investigated the underlying hypothesis that antagonists of HIV-1 Envelope (Env) gp120 and host cell co-receptor (CoR) proteins can be covalently joined into bifunctional synergistic combinations that will improve antiviral. A synthetic protocol was established to covalently combine a CCR5 small molecule antagonist and a gp120 peptide triazole antagonist to form the bifunctional chimera. Importantly, the chimeric inhibitor preserved the specific targeting properties of the two separate chimera components, and at the same time exhibited low to sub-nanomolar potencies, in inhibiting cell infection by different pseudoviruses, that were substantially greater than those of a non-covalent mixture of individual components...
May 16, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29762173/a-defucosylated-bispecific-multivalent-molecule-exhibits-broad-hiv-1-neutralizing-activity-and-enhanced-adcc-against-reactivated-hiv-1-latently-infected-cells
#5
Desheng Kong, Yan Wang, Ping Ji, Wei Li, Tianlei Ying, Jinghe Huang, Chen Wang, Yanling Wu, Yanping Wang, Weizao Chen, Yanling Hao, Kunxue Hong, Yiming Shao, Dimiter S Dimitrov, Shibo Jiang, Liying Ma
OBJECTIVE: Current treatments cannot completely eradicate HIV-1 owing to the presence of latently infected cells which harbor transcriptionally silent HIV-1. However, defucosylated antibodies can readily kill latently infected cells after their activation to express envelope glycoprotein (Env) through antibody-dependent cellular cytotoxicity (ADCC). We herein aimed to test a defucosylated bispecific multivalent molecule consisting of domain-antibody and single-domain CD4, LSEVh-LS-F, for its HIV-1 neutralizing activity and ADCC against the reactivated latently infected cells, compared with the non-defucosylated molecule LSEVh-LS...
May 11, 2018: AIDS
https://www.readbyqxmd.com/read/29756455/characterization-of-the-transmitted-virus-in-an-ongoing-hiv-1-epidemic-driven-by-injecting-drug-use
#6
Elena Dukhovlinova, Alexey Masharsky, Aleksandra Vasileva, Alessandro Porrello, Shuntai Zhou, Olga Toussova, Sergei Verevochkin, Ekaterina Akulova, Dmitrij Frishman, David Montefiori, Celia Labranche, Irving Hoffman, William Miller, Myron S Cohen, Andrei Kozlov, Ronald Swanstrom
Understanding features of the HIV-1 transmission process have the potential to inform biological interventions for prevention. We have examined the transmitted virus in a cohort of people who inject drugs and who are at risk of HIV-1 infection through blood contamination when injecting in a group. This study focused on seven newly infected participants in St. Petersburg, Russia, who were in acute or early infection. We used end-point dilution PCR to amplify single viral genomes to assess the complexity of the transmitted virus...
May 14, 2018: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29749030/a-new-therapeutic-approach-for-type-1-diabetes-rationale-for-gnbac1-an-anti-herv-w-env-monoclonal-antibody
#7
REVIEW
Francois Curtin, Corinne Bernard, Sandrine Levet, Hervé Perron, Hervé Porchet, Julie Médina, Sam Malpass, David Lloyd, Richard Simpson
We describe a newly identified therapeutic target for type 1 diabetes: an envelope protein of endogenous retroviral origin called Human Endogenous Retrovirus W Envelope (HERV-W-Env). HERV-W-Env was found to be detected in the blood of around 60% of type 1 diabetes (T1D) patients and is expressed in acinar pancreatic cells of 75% of T1D patients at post-mortem examination. Preclinical experiments showed that this protein displays direct cytotoxicity on human β-islet cells. In vivo HERV-W-Env impairs the insulin and glucose metabolism in transgenic mice expressing HERV-W-Env...
May 10, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29748537/single-molecule-fate-of-hiv-1-envelope-reveals-late-stage-viral-lattice-incorporation
#8
Carmen A Buttler, Nairi Pezeshkian, Melissa V Fernandez, Jesse Aaron, Sofya Norman, Eric O Freed, Schuyler B van Engelenburg
Human immunodeficiency virus type 1 (HIV-1) assembly occurs on the inner leaflet of the host cell plasma membrane, incorporating the essential viral envelope glycoprotein (Env) within a budding lattice of HIV-1 Gag structural proteins. The mechanism by which Env incorporates into viral particles remains poorly understood. To determine the mechanism of recruitment of Env to assembly sites, we interrogate the subviral angular distribution of Env on cell-associated virus using multicolor, three-dimensional (3D) superresolution microscopy...
May 10, 2018: Nature Communications
https://www.readbyqxmd.com/read/29743369/intrastructural-help-harnessing-t-helper-cells-induced-by-licensed-vaccines-for-improvement-of-hiv-env-antibody-responses-to-virus-like-particle-vaccines
#9
Hassan Elsayed, Ghulam Nabi, William J McKinstry, Keith K Khoo, Johnson Mak, Andres M Salazar, Matthias Tenbusch, Vladimir Temchura, Klaus Überla
Induction of persistent antibody responses by vaccination is generally thought to depend on efficient help by T follicular helper cells. Since the T helper cell response to HIV Env may not be optimal, we explored the possibility to improve the HIV Env antibody response to virus-like particle (VLP) vaccines by recruiting T helper cells induced by a commonly-used licensed vaccines to provide help for Env-specific B cells. B cells specific for the surface protein of a VLP can internalize the entire VLP and thus present peptides derived from the surface and core proteins on their MHC-II molecules...
May 9, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29743357/the-antiviral-activity-of-the-cellular-glycoprotein-lgals3bp-90k-is-species-specific
#10
Veronika Lodermeyer, George Ssebyatika, Vânia Passos, Aparna Ponnurangam, Angelina Malassa, Ellen Ewald, Christina M Stürzel, Frank Kirchhoff, Margalida Rotger, Christine S Falk, Amalio Telenti, Thomas Krey, Christine Goffinet
Cellular antiviral proteins interfere with distinct steps of replication cycles of viruses. The galectin 3 binding protein (LGALS3BP, also known as 90K) was previously shown to lower the infectivity of nascent HIV-1 virions when expressed in virus-producing cells. This antiviral effect was accompanied by impaired gp160Env processing and reduced viral incorporation of mature Env glycoproteins. Here, we examined the ability of 90K orthologs from primate species to reduce particle infectivity of distinct lentiviruses...
May 9, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29703241/human-immunodeficiency-virus-type-1-hiv-1-mediated-neuroinflammation-dysregulates-neurogranin-and-induces-synaptodendritic-injury
#11
Debjani Guha, Marc C E Wagner, Velpandi Ayyavoo
BACKGROUND: Human immunodeficiency virus type 1 (HIV-1)-associated neurocognitive disorder (HAND) is a common outcome of a majority of HIV-1-infected subjects and is associated with synaptodendritic damage. Neurogranin (Ng), a postsynaptic protein, and calmodulin (CaM) are two important players of synaptic integrity/functions. The biological role of Ng in the context of HAND is unknown. METHODS: We compared the expression of Ng in frontal cortex (FC) tissues from control and HIV-1-positive subjects with and without HAND by immunohistochemistry, western blot, and qRT-PCR...
April 27, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29698406/generation-and-characterization-of-a-bivalent-protein-boost-for-future-clinical-trials-hiv-1-subtypes-cr01_ae-and-b-gp120-antigens-with-a-potent-adjuvant
#12
Yingxia Wen, Hung V Trinh, Christine E Linton, Chiara Tani, Nathalie Norais, DeeAnn Martinez-Guzman, Priyanka Ramesh, Yide Sun, Frank Situ, Selen Karaca-Griffin, Christopher Hamlin, Sayali Onkar, Sai Tian, Susan Hilt, Padma Malyala, Rushit Lodaya, Ning Li, Gillis Otten, Giuseppe Palladino, Kristian Friedrich, Yukti Aggarwal, Celia LaBranche, Ryan Duffy, Xiaoying Shen, Georgia D Tomaras, David C Montefiori, William Fulp, Raphael Gottardo, Brian Burke, Jeffrey B Ulmer, Susan Zolla-Pazner, Hua-Xin Liao, Barton F Haynes, Nelson L Michael, Jerome H Kim, Mangala Rao, Robert J O'Connell, Andrea Carfi, Susan W Barnett
The RV144 Phase III clinical trial with ALVAC-HIV prime and AIDSVAX B/E subtypes CRF01_AE (A244) and B (MN) gp120 boost vaccine regime in Thailand provided a foundation for the future development of improved vaccine strategies that may afford protection against the human immunodeficiency virus type 1 (HIV-1). Results from this trial showed that immune responses directed against specific regions V1V2 of the viral envelope (Env) glycoprotein gp120 of HIV-1, were inversely correlated to the risk of HIV-1 infection...
2018: PloS One
https://www.readbyqxmd.com/read/29678797/subtle-differences-in-selective-pressures-applied-on-the-envelope-gene-of-hiv-1-in-pregnant-versus-non-pregnant-women
#13
Doris G Ransy, Etienne Lord, Martine Caty, Normand Lapointe, Marc Boucher, Abdoulaye Baniré Diallo, Hugo Soudeyns
Pregnancy is associated with modulations of maternal immunity that contribute to foeto-maternal tolerance. To understand whether and how these alterations impact antiviral immunity, a detailed cross-sectional analysis of selective pressures exerted on HIV-1 envelope amino-acid sequences was performed in a group of pregnant (n = 32) and non-pregnant (n = 44) HIV-infected women in absence of treatment with antiretroviral therapy (ART). Independent of HIV-1 subtype, p-distance, dN and dS were all strongly correlated with one another but were not significantly different in pregnant as compared to non-pregnant patients...
April 17, 2018: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/29669838/effects-of-adjuvants-on-hiv-1-envelope-glycoprotein-sosip-trimers-in-vitro
#14
Gabriel Ozorowski, Albert Cupo, Michael Golabek, Michelle LoPiccolo, Thomas A Ketas, Matt Cavallary, Christopher A Cottrell, P J Klasse, Andrew B Ward, John P Moore
Native-like, soluble, recombinant SOSIP trimers of various designs and based on several env genes of human immunodeficiency virus type 1 (HIV-1) are being tested as immunogens in different animal models. These experiments almost always involve co-formulating the trimers with an adjuvant to boost the magnitude of the immune responses. One factor relevant to the choice of an adjuvant is that it should not physically damage the immunogen or impede its ability to present relevant epitopes. As examples, an adjuvant formulation that includes harsh detergents could disrupt the structural integrity of a trimer, and any charged compounds in the formulation could bind to counter-charged regions of the trimer and physically occlude nearby epitopes...
April 18, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29664204/characterization-and-epitope-mapping-of-a-panel-of-monoclonal-antibodies-against-hiv-1-matrix-protein
#15
Zhiqing Zhang, Feng Zhang, Shimeng Bai, Jiaming Qiao, Honglin Shen, Fang Huang, Shuangquan Gao, Shaowei Li, Ying Gu, Ningshao Xia
The HIV-1 Gag precursor protein (p55) is the main structural protein comprising the matrix (MA/p17), capsid (CA/p24), and nucleocapsid (NC/p7) proteins, and is uniquely responsible for virion assembly within the virus life cycle. The MA protein plays a critical role in plasma membrane targeting and envelope glycoprotein (Env) uptake during virion assembly. Yet, when viral infection occurs, the MA protein may also be involved in virion uncoating, dissociating from the plasma membrane, and participating in the nuclear importation process...
April 17, 2018: Biotechnology and Applied Biochemistry
https://www.readbyqxmd.com/read/29643249/neutralizing-antibody-responses-following-long-term-vaccination-with-hiv-1-env-gp140-in-guinea-pigs
#16
Christine A Bricault, James M Kovacs, Alexander Badamchi-Zadeh, Krisha McKee, Jennifer L Shields, Bronwyn M Gunn, George H Neubauer, Fadi Ghantous, Julia Jennings, Lindsey Gillis, James Perry, Joseph P Nkolola, Galit Alter, Bing Chen, Kathryn E Stephenson, Nicole Doria-Rose, John R Mascola, Michael S Seaman, Dan H Barouch
A vaccination regimen capable of eliciting potent and broadly neutralizing antibodies (bNAbs) remains an unachieved goal of the HIV-1 vaccine field. Here we report the immunogenicity of longitudinal prime/boost vaccination regimens over a period of 200 weeks in guinea pigs with a panel of HIV-1 envelope (Env) gp140 protein immunogens. We assessed vaccine regimens that included a monovalent clade C gp140 regimen (C97), a tetravalent regimen consisting of four clade C gp140s (4C), and a tetravalent regimen consisting of a clade A, B, C, and mosaic gp140 (ABCM)...
April 11, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29624497/pseudotyping-of-hiv-1-with-human-t-lymphotropic-virus-1-htlv-1-envelope-glycoprotein-during-hiv-1-htlv-1-coinfection-facilitates-direct-hiv-1-infection-of-female-genital-epithelial-cells-implications-for-sexual-transmission-of-hiv-1
#17
Yuyang Tang, Alvin M George, Oksana Petrechko, Franklin J Nouvet, Stephanie D Sweet, Yuetsu Tanaka, Brian S Imbiakha, Guochun Jiang, Wei Gao, Kathryn Anastos, James E K Hildreth
Female genital epithelial cells cover the genital tract and provide the first line of protection against infection with sexually transmitted pathogenic viruses. These cells normally are impervious to HIV-1. We report that coinfection of cells by HIV-1 and another sexually transmitted virus, human T-lymphotropic virus 1 (HTLV-1), led to production of HIV-1 that had expanded cell tropism and was able to directly infect primary vaginal and cervical epithelial cells. HIV-1 infection of epithelial cells was blocked by neutralizing antibodies against the HTLV-1 envelope (Env) protein, indicating that the infection was mediated through HTLV-1 Env pseudotyping of HIV-1...
April 25, 2018: MSphere
https://www.readbyqxmd.com/read/29618899/hypothetical-endogenous-siv-like-antigens-in-mauritian-cynomolgus-macaques
#18
Hongzhao Li, Lin Li, Lewis R Liu, Robert W Omange, Nikki Toledo, Mohammad Abul Kashem, Yan Hai, Binhua Liang, Francis A Plummer, Ma Luo
Simian immunodeficiency virus (SIV) infection of Mauritian cynomolgus macaques (MCMs) is an increasingly important nonhuman primate model for HIV vaccine research. We previously reported that in MCMs anti-SIV antibodies can be naturally developed without exogenous infection or vaccination, and that a vaccine targeting SIV protease cleavage sites (PCS) can cross-induce antibodies to non-PCS SIV antigens. We speculate that this is potentially caused by the existence of endogenous SIV-like antigens. External stimuli (such as environmental factors and vaccination) may induce expression of endogenous SIV-like antigens to elicit these antibodies...
2018: Bioinformation
https://www.readbyqxmd.com/read/29617816/immunization-with-a-novel-human-type-5-adenovirus-vectored-vaccine-expressing-the-premembrane-and-envelope-proteins-of-zika-virus-provides-consistent-and-sterilizing-protection-in-multiple-immunocompetent-and-immunocompromised-animal-models
#19
Qiang Guo, Jasper Fuk-Woo Chan, Vincent Kwok-Man Poon, Shipo Wu, Chris Chung-Sing Chan, Lihua Hou, Cyril Chik-Yan Yip, Changpeng Ren, Jian-Piao Cai, Mengsu Zhao, Anna Jinxia Zhang, Xiaohong Song, Kwok-Hung Chan, Busen Wang, Kin-Hang Kok, Yanbo Wen, Kwok-Yung Yuen, Wei Chen
Background: Zika virus (ZIKV) infection may be associated with severe complications and disseminated via both vector-borne and non-vector-borne routes. Adenovirus-vectored vaccines represent a favorable controlling measure for the ZIKV epidemic as they have been shown to be safe, immunogenic, and rapidly generable for other emerging viral infections. Evaluations of two previously reported adenovirus-vectored ZIKV vaccines were performed using non-lethal animal models and/or non-epidemic ZIKV strain...
March 29, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29603839/humoral-immunity-response-to-herv-k-w-differentiates-between-amyotrophic-lateral-sclerosis-and-other-neurological-diseases
#20
Giannina Arru, Giuseppe Mameli, Giovanni Andrea Deiana, Anna Laura Rassu, Rosanna Piredda, Elia Sechi, Elisa Caggiu, Marco Bo, Enri Nako, Daniele Urso, Sara Mariotto, Sergio Ferrari, Gianluigi Zanusso, Salvatore Monaco, GianPietro Sechi, Leonardo A Sechi
BACKGROUND AND PURPOSE: Human endogenous retroviruses-K/W seem play a role in fostering and exacerbation of some neurological diseases, including amyotrophic lateral sclerosis (ALS). Given these findings, we investigated the immunity response against HERV-K and HERV-W envelope surface (env-su) glycoprotein antigens in serum and cerebrospinal fluid (CSF) of ALS, multiple sclerosis (MS) and Alzheimer's disease (AD) patients, and in healthy controls (HCs). METHODS: Four antigenic peptides derived respectively from HERV-K and HERV-W env surface proteins were studied in twenty-one definite or probable ALS, twenty-six possible or definite relapsing-remitting (RR) MS, eighteen patients with AD and thirty-nine HCs...
March 31, 2018: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
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