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https://www.readbyqxmd.com/read/29038280/targeting-human-cytomegalovirus-infected-cells-by-redirecting-t-cells-using-an-anti-cd3-anti-gb-bispecific-antibody
#1
Weixu Meng, Aimin Tang, Xiaohua Ye, Xun Gui, Leike Li, Xuejun Fan, Robbie D Schultz, Daniel C Freed, Sha Ha, Dai Wang, Ningyan Zhang, Tong-Ming Fu, Zhiqiang An
Host immune response to human cytomegalovirus (HCMV) is effective against HCMV reactivation from latency although not sufficient to clear the virus. T cells are primarily responsible for control of the viral reactivation. When host immune system is compromised, as in transplant recipients with immunosuppression, HCMV reactivation and progressive infection can cause serious morbidity and mortality. Adoptive T cell therapy is effective for control of HCMV infection in transplant recipients. However, it is a highly personalized therapeutic regimen, and difficult to implement in routine clinical practice...
October 16, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29035787/identification-of-n-linked-glycosylation-sites-in-the-spike-protein-and-their-functional-impact-on-the-replication-and-infectivity-of-coronavirus-infectious-bronchitis-virus-in-cell-culture
#2
Jie Zheng, Yoshiyuki Yamada, To Sing Fung, Mei Huang, Raymond Chia, Ding Xiang Liu
Spike (S) glycoprotein on the viral envelope is the main determinant of infectivity. The S protein of coronavirus infectious bronchitis virus (IBV) contains 29 putative asparagine(N)-linked glycosylation sites. These post-translational modifications may assist in protein folding and play important roles in the functionality of S protein. In this study, we used bioinformatics tools to predict N-linked glycosylation sites and to analyze their distribution in IBV strains and variants. Among these sites, 8 sites were confirmed in the S protein extracted from partially purified virus particles by proteomics approaches...
October 13, 2017: Virology
https://www.readbyqxmd.com/read/29031163/ebola-virus-requires-phosphatidylinositol-3-5-bisphosphate-production-for-efficient-viral-entry
#3
Shirley Qiu, Anders Leung, Yuxia Bo, Robert A Kozak, Sai Priya Anand, Corina Warkentin, Fabiola D R Salambanga, Jennifer Cui, Gary Kobinger, Darwyn Kobasa, Marceline Côté
For entry, Ebola virus (EBOV) requires the interaction of its viral glycoprotein with the cellular protein Niemann-Pick C1 (NPC1) which resides in late endosomes and lysosomes. How EBOV is trafficked and delivered to NPC1 and whether this is positively regulated during entry remain unclear. Here, we show that the PIKfyve-ArPIKfyve-Sac3 cellular complex, which is involved in the metabolism of phosphatidylinositol (3,5) bisphosphate (PtdIns(3,5)P2), is critical for EBOV infection. Although the expression of all subunits of the complex was required for efficient entry, PIKfyve kinase activity was specifically critical for entry by all pathogenic filoviruses...
October 11, 2017: Virology
https://www.readbyqxmd.com/read/28963576/development-and-evaluation-of-a-simple-and-effective-rt-qpcr-inhibitory-assay-for-detection-of-the-efficacy-of-compounds-towards-hiv-reverse-transcriptase
#4
Francesca Marino-Merlo, Caterina Frezza, Emanuela Papaianni, Elena Valletta, Antonio Mastino, Beatrice Macchi
Assessing the actual efficacy of compounds to directly inhibit HIV reverse transcriptase (RT) activity is a main goal in preclinical antiretroviral studies. Our previous studies demonstrated that the effects of inhibitor compounds towards HIV-RT could be efficiently assessed through a simple cell-free assay based on conventional reverse transcription PCR. In the present study, we describe a modified variant of our assay, termed RT real-time quantitative PCR inhibitory assay (RT-qPCR-IA), in which the ability of compounds to restrict the complementary DNA (cDNA) generation by HIV-RT using a specific RNA template is performed by the real-time technique, in order to improve both accuracy and sensitivity of the method...
September 30, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28931689/vaccination-with-recombinant-parainfluenza-virus-5-expressing-neuraminidase-protects-against-homologous-and-heterologous-influenza-virus-challenge
#5
Alaina J Mooney, Jon D Gabbard, Zhuo Li, Daniel A Dlugolenski, Scott K Johnson, Ralph A Tripp, Biao He, S Mark Tompkins
Seasonal human influenza virus continues to cause morbidity and mortality annually, and highly pathogenic avian influenza (HPAI) along with other emerging influenzas continue to pose pandemic threats. Vaccination is considered the most effective measure for controlling influenza; however, current strategies rely on a precise vaccine match with currently circulating virus strains for efficacy, requiring constant surveillance and regular development of matched vaccines. Current vaccines focus on eliciting specific antibody responses against the hemagglutinin (HA) surface glycoprotein; however, the diversity of HAs across species and antigenic drift of circulating strains enables evasion of virus-inhibiting antibody responses, resulting in vaccine failure...
September 20, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28905885/long-term-correction-of-hemophilia-a-mice-following-lentiviral-mediated-delivery-of-an-optimized-canine-factor-viii-gene
#6
J M Staber, M J Pollpeter, C-G Anderson, M Burrascano, A L Cooney, P L Sinn, D T Rutkowski, W C Raschke, P B McCray
Current therapies for hemophilia A include frequent prophylactic or on-demand intravenous factor treatments which are costly, inconvenient and may lead to inhibitor formation. Viral vector delivery of factor VIII (FVIII) cDNA has the potential to alleviate the debilitating clotting defects. Lentiviral-based vectors delivered to murine models of hemophilia A mediate phenotypic correction. However, a limitation of lentiviral-mediated FVIII delivery is inefficient transduction of target cells. Here, we engineer a feline immunodeficiency virus (FIV) -based lentiviral vector pseudotyped with the baculovirus GP64 envelope glycoprotein to mediate efficient gene transfer to mouse hepatocytes...
September 14, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28878084/human-herpesvirus-8-interleukin-6-interacts-with-calnexin-cycle-components-and-promotes-protein-folding
#7
Daming Chen, Qiwang Xiang, John Nicholas
Viral interleukin-6 (vIL-6) encoded by human herpesvirus 8 (HHV-8) is believed to contribute via mitogenic, survival, and angiogenic activities to HHV-8-associated Kaposi's sarcoma, primary effusion lymphoma (PEL), and multicentric Castleman's disease through autocrine or paracrine mechanisms during latency or productive replication. There is direct evidence that vIL-6 promotes latently infected PEL cell viability and proliferation and also viral productive replication in PEL and endothelial cells. These activities are mediated largely through endoplasmic reticulum (ER)-localized vIL-6, which can induce signal transduction via the gp130 signaling receptor, activating mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription (STAT) signaling, and interactions of vIL-6 with the ER membrane protein vitamin K epoxide reductase complex subunit 1 variant 2 (VKORC1v2)...
September 6, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28835504/attenuated-human-parainfluenza-virus-type-1-hpiv1-expressing-the-respiratory-syncytial-virus-rsv-fusion-f-glycoprotein-from-an-added-gene-effects-of-pre-fusion-stabilization-and-packaging-of-rsv-f
#8
Xiang Liu, Bo Liang, Joan Ngwuta, Xueqiao Liu, Sonja Surman, Matthias Lingemann, Peter D Kwong, Barney S Graham, Peter L Collins, Shirin Munir
Human respiratory syncytial virus (RSV) is the most prevalent worldwide cause of severe respiratory tract infection in infants and young children. Human parainfluenza virus type 1 (HPIV1) also causes severe pediatric respiratory illness, especially croup. Both viruses lack vaccines. Here, we describe the preclinical development of a bivalent RSV/HPIV1 vaccine based on a recombinant HPIV1 vector, attenuated by a stabilized mutation, that expresses RSV F protein modified for increased stability in the pre-fusion (pre-F) conformation by previously-described disulfide bond (DS) and hydrophobic cavity-filling (Cav1) mutations...
August 23, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28808690/the-hemagglutinin-esterase-fusion-glycoprotein-is-a-primary-determinant-of-the-exceptional-thermal-and-acid-stability-of-influenza-d-virus
#9
Jieshi Yu, Busha Hika, Runxia Liu, Zizhang Sheng, Ben M Hause, Feng Li, Dan Wang
Influenza D virus (IDV) is unique among four types of influenza viruses in that it utilizes cattle as a primary reservoir. The thermal and acid stability of IDV were examined and directly compared with those of influenza A virus (IAV), influenza B virus (IBV), and influenza C virus (ICV). The results of our experiments demonstrated that only IDV had a high residual infectivity (~2.5 log units of 50% tissue culture infective dose [TCID50]/ml) after a 60-min exposure to 53°C in solution at a neutral pH, and remarkably, IDV retained this infectivity even after exposure to 53°C for 120 min...
July 2017: MSphere
https://www.readbyqxmd.com/read/28721397/hivis-dna-or-hivisopt-dna-priming-followed-by-cmdr-vaccinia-based-boosts-induce-both-humoral-and-cellular-murine-immune-responses-to-hiv
#10
J Hinkula, S Petkov, K Ljungberg, D Hallengärd, A Bråve, M Isaguliants, T Falkeborn, S Sharma, V Liakina, M Robb, M Eller, B Moss, G Biberfeld, E Sandström, C Nilsson, K Markland, P Blomberg, B Wahren
BACKGROUND: In order to develop a more effective prophylactic HIV-1 vaccine it is important optimize the components, improve Envelope glycoprotein immunogenicity as well as to explore prime-boost immunization schedules. It is also valuable to include several HIV-1 subtype antigens representing the world-wide epidemic. METHODS: HIVIS-DNA plasmids which include Env genes of subtypes A, B and C together with Gag subtypes A and B and RTmut/Rev of subtype B were modified as follows: the Envelope sequences were shortened, codon optimized, provided with an FT4 sequence and an immunodominant region mutated...
June 2017: Heliyon
https://www.readbyqxmd.com/read/28714909/the-interplay-between-the-host-receptor-and-influenza-virus-hemagglutinin-and-neuraminidase
#11
REVIEW
Lauren Byrd-Leotis, Richard D Cummings, David A Steinhauer
The hemagglutinin (HA) and neuraminidase (NA) glycoproteins of influenza A virus are responsible for the surface interactions of the virion with the host. Entry of the virus is mediated by functions of the HA: binding to cellular receptors and facilitating fusion of the virion membrane with the endosomal membrane. The HA structure contains receptor binding sites in the globular membrane distal head domains of the trimer, and the fusion machinery resides in the stem region. These sites have specific characteristics associated with subtype and host, and the differences often define species barriers...
July 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28650722/optimized-dna-vaccine-enhanced-by-adjuvant-il28b-induces-protective-immune-responses-against-herpes-simplex-virus-type-2-in-mice
#12
Yan Zhou, Ziyan Wang, Yongqing Xu, Zeqiang Zhang, Rui Hua, Wei Liu, Chunlai Jiang, Yan Chen, Wenying Yang, Wei Kong
Antigen-specific immune responses determine the efficacy of herpes simplex virus type 2 (HSV-2) vaccines. To optimize the immunogenicity of the antigen gD2, we developed the gD2ΔUL25 DNA vaccine encoding HSV-2 glycoprotein D and UL25 gene encoding viral capsid vertex proteins in this study. The gD2 and gD2ΔUL25 DNA vaccines were compared with formalin-inactivated HSV-2 (FI-HSV-2), and results showed a greater protective immune response induced by gD2ΔUL25 than by gD2. Therefore, gD2ΔUL25 was chosen to evaluate further using the IL28B adjuvant...
October 2017: Viral Immunology
https://www.readbyqxmd.com/read/28631601/viral-genes-and-cellular-markers-associated-with-neurological-complications-during-herpesvirus-infections
#13
Carine L Holz, Rahul K Nelli, M Eilidh Wilson, Lila M Zarski, Walid Azab, Rachel Baumgardner, Nikolaus Osterrieder, Anthony Pease, Liangliang Zhang, Sarah Hession, Lutz S Goehring, Stephen B Hussey, Gisela Soboll Hussey
Despite the importance of neurological disorders associated with herpesviruses, the mechanism by which these viruses influence the central nervous system (CNS) has not been definitively established. Owing to the limitations of studying neuropathogenicity of human herpesviruses in their natural host, many aspects of their pathogenicity and immune response are studied in animal models. Here, we present an important model system that enables studying neuropathogenicity of herpesviruses in the natural host. Equine herpesvirus type 1 (EHV-1) is an alphaherpesvirus that causes a devastating neurological disease (EHV-1 myeloencephalopathy; EHM) in horses...
June 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28628828/sensitivity-to-bst-2-restriction-correlates-with-orthobunyavirus-host-range
#14
Mariana Varela, Ilaria M Piras, Catrina Mullan, Xiaohong Shi, Natasha L Tilston-Lunel, Rute Maria Pinto, Aislynn Taggart, Stephen R Welch, Stuart J D Neil, Felix Kreher, Richard M Elliott, Massimo Palmarini
Orthobunyaviruses include several recently emerging viruses of significant medical and veterinary importance. There is currently very limited understanding on what determines the host species range of these pathogens. In this study we discovered that BST-2/tetherin restricts orthobunyavirus replication in a host-specific manner. We show that viruses with human tropism (Oropouche virus and La Crosse virus) are restricted by sheep BST-2 but not by the human orthologue, while viruses with ruminant tropism (Schmallenberg virus and others) are restricted by human BST-2 but not by the sheep orthologue...
September 2017: Virology
https://www.readbyqxmd.com/read/28604661/computational-design-of-trimeric-influenza-neutralizing-proteins-targeting-the-hemagglutinin-receptor-binding-site
#15
Eva-Maria Strauch, Steffen M Bernard, David La, Alan J Bohn, Peter S Lee, Caitlin E Anderson, Travis Nieusma, Carly A Holstein, Natalie K Garcia, Kathryn A Hooper, Rashmi Ravichandran, Jorgen W Nelson, William Sheffler, Jesse D Bloom, Kelly K Lee, Andrew B Ward, Paul Yager, Deborah H Fuller, Ian A Wilson, David Baker
Many viral surface glycoproteins and cell surface receptors are homo-oligomers, and thus can potentially be targeted by geometrically matched homo-oligomers that engage all subunits simultaneously to attain high avidity and/or lock subunits together. The adaptive immune system cannot generally employ this strategy since the individual antibody binding sites are not arranged with appropriate geometry to simultaneously engage multiple sites in a single target homo-oligomer. We describe a general strategy for the computational design of homo-oligomeric protein assemblies with binding functionality precisely matched to homo-oligomeric target sites...
July 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28544850/pcpp-adjuvanted-respiratory-syncytial-virus-rsv-sf-subunit-vaccine-self-assembled-supramolecular-complexes-enable-enhanced-immunogenicity-and-protection
#16
Corinne Cayatte, Alexander Marin, Gaurav Manohar Rajani, Kirsten Schneider-Ohrum, Angie Snell Bennett, Jason D Marshall, Alexander K Andrianov
PCPP, a well-defined polyphosphazene macromolecule, has been studied as an immunoadjuvant for a soluble form of the postfusion glycoprotein of respiratory syncytial virus (RSV sF), which is an attractive vaccine candidate for inducing RSV-specific immunity in mice and humans. We demonstrate that RSV sF-PCPP formulations induce high neutralization titers to RSV comparable to alum formulations even at a low PCPP dose and protect animals against viral challenge both in the lung and in the upper respiratory tract...
June 7, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28542541/varicella-zoster-virus-glycoprotein-c-increases-chemokine-mediated-leukocyte-migration
#17
Víctor González-Motos, Carina Jürgens, Birgit Ritter, Kai A Kropp, Verónica Durán, Olav Larsen, Anne Binz, Werner J D Ouwendijk, Tihana Lenac Rovis, Stipan Jonjic, Georges M G M Verjans, Beate Sodeik, Thomas Krey, Rudolf Bauerfeind, Thomas F Schulz, Benedikt B Kaufer, Ulrich Kalinke, Amanda E I Proudfoot, Mette M Rosenkilde, Abel Viejo-Borbolla
Varicella zoster virus (VZV) is a highly prevalent human pathogen that establishes latency in neurons of the peripheral nervous system. Primary infection causes varicella whereas reactivation results in zoster, which is often followed by chronic pain in adults. Following infection of epithelial cells in the respiratory tract, VZV spreads within the host by hijacking leukocytes, including T cells, in the tonsils and other regional lymph nodes, and modifying their activity. In spite of its importance in pathogenesis, the mechanism of dissemination remains poorly understood...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28542478/structural-basis-of-nectin-1-recognition-by-pseudorabies-virus-glycoprotein-d
#18
An Li, Guangwen Lu, Jianxun Qi, Lili Wu, Kegong Tian, Tingrong Luo, Yi Shi, Jinghua Yan, George F Gao
An early and yet indispensable step in the alphaherpesvirus infection is the engagement of host receptors by the viral envelope glycoprotein D (gD). Of the thus-far identified gD receptors, nectin-1 is likely the most effective in terms of its wide usage by multiple alphaherpesviruses for cell entry. The molecular basis of nectin-1 recognition by the gD protein is therefore an interesting scientific question in the alphaherpesvirus field. Previous studies focused on the herpes simplex virus (HSV) of the Simplexvirus genus, for which both the free gD structure and the gD/nectin-1 complex structure were reported at high resolutions...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28525755/antibodies-from-a-human-survivor-define-sites-of-vulnerability-for-broad-protection-against-ebolaviruses
#19
Anna Z Wec, Andrew S Herbert, Charles D Murin, Elisabeth K Nyakatura, Dafna M Abelson, J Maximilian Fels, Shihua He, Rebekah M James, Marc-Antoine de La Vega, Wenjun Zhu, Russell R Bakken, Eileen Goodwin, Hannah L Turner, Rohit K Jangra, Larry Zeitlin, Xiangguo Qiu, Jonathan R Lai, Laura M Walker, Andrew B Ward, John M Dye, Kartik Chandran, Zachary A Bornholdt
Experimental monoclonal antibody (mAb) therapies have shown promise for treatment of lethal Ebola virus (EBOV) infections, but their species-specific recognition of the viral glycoprotein (GP) has limited their use against other divergent ebolaviruses associated with human disease. Here, we mined the human immune response to natural EBOV infection and identified mAbs with exceptionally potent pan-ebolavirus neutralizing activity and protective efficacy against three virulent ebolaviruses. These mAbs recognize an inter-protomer epitope in the GP fusion loop, a critical and conserved element of the viral membrane fusion machinery, and neutralize viral entry by targeting a proteolytically primed, fusion-competent GP intermediate (GPCL) generated in host cell endosomes...
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28520963/humoral-and-innate-antiviral-immunity-as-tools-to-clear-persistent-hiv-infection
#20
REVIEW
Guido Ferrari, Justin Pollara, Georgia D Tomaras, Barton F Haynes
Human immunodeficiency virus (HIV) type 1 uses the CD4 molecule as its principal receptor to infect T cells. HIV-1 integrates its viral genome into the host cell, leading to persistent infection wherein HIV-1 can remain transcriptionally silent in latently infected CD4+ T cells. On reactivation of replication-competent provirus, HIV-1 envelope glycoproteins (Env) are expressed and accumulate on the cell surface, allowing infected cells to be detected and targeted by endogenous immune responses or immune interventions...
March 15, 2017: Journal of Infectious Diseases
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