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https://www.readbyqxmd.com/read/28103319/an-hsv-2-trivalent-vaccine-is-immunogenic-in-rhesus-macaques-and-highly-efficacious-in-guinea-pigs
#1
Sita Awasthi, Lauren M Hook, Carolyn E Shaw, Bapi Pahar, Jacob A Stagray, David Liu, Ronald S Veazey, Harvey M Friedman
A genital herpes vaccine is urgently needed to prevent pain and suffering, reduce the incidence of neonatal herpes, and decrease the risk of HIV acquisition and transmission that accompanies genital infection. We evaluated a trivalent HSV-2 subunit antigen vaccine administered with CpG and alum in rhesus macaques and guinea pigs. The vaccine contains glycoproteins C, D and E (gC2, gD2, gE2) to block virus entry by gD2 and immune evasion by gC2 and gE2. In rhesus macaques, the trivalent vaccine induced plasma and mucosa neutralizing antibodies, antibodies that block gC2 and gE2 immune evasion activities, and stimulated CD4 T cell responses...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28101536/host-range-restriction-of-insect-specific-flaviviruses-occurs-at-several-levels-of-the-viral-life-cycle
#2
Sandra Junglen, Marvin Korries, Wolfgang Grasse, Janett Wieseler, Anne Kopp, Kyra Hermanns, Moises León-Juárez, Christian Drosten, Beate Mareike Kümmerer
The genus Flavivirus contains emerging arthropod-borne viruses (arboviruses) infecting vertebrates, as well as insect-specific viruses (ISVs) (i.e., viruses whose host range is restricted to insects). ISVs are evolutionary precursors to arboviruses. Knowledge of the nature of the ISV infection block in vertebrates could identify functions necessary for the expansion of the host range toward vertebrates. Mapping of host restrictions by complementation of ISV and arbovirus genome functions could generate knowledge critical to predicting arbovirus emergence...
January 2017: MSphere
https://www.readbyqxmd.com/read/28100619/functional-analysis-of-hcv-envelope-protein-e1-using-a-trans-complementation-system-reveals-a-dual-role-of-a-putative-fusion-peptide-of-e1-in-both-hcv-entry-and-morphogenesis
#3
Yimin Tong, Xiaojing Chi, Wei Yang, Jin Zhong
: Hepatitis C virus (HCV) is an enveloped RNA virus belonging to the Flaviviridae family. It mainly infects human hepatocytes and causes chronic liver diseases including cirrhosis and cancer. HCV encodes two envelope proteins E1 and E2 that form a heterodimer and mediate virus entry. While E2 has been extensively studied, less has been done so for E1, and its role in HCV life cycle still needs to be elucidated. Here we developed a new cell culture model for HCV infection based on trans-complementation of E1...
January 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28100616/the-v3-loop-of-hiv-1-env-determines-viral-susceptibility-to-ifitm3-impairment-of-viral-infectivity
#4
Yimeng Wang, Qinghua Pan, Shilei Ding, Zhen Wang, Jingyou Yu, Andrés Finzi, Shan-Lu Liu, Chen Liang
: Interferon inducible transmembrane proteins (IFITMs) inhibit a broad spectrum of viruses including HIV-1. IFITM proteins deter HIV-1 entry when expressed in target cells and also impair HIV-1 infectivity when expressed in virus producer cells. However, little is known about how viruses resist IFITM inhibition. In this study, we have investigated the susceptibilities of different primary isolates of HIV-1 to the inhibition of viral infectivity by IFITMs. Our results demonstrate that the infectivity of different HIV-1 primary isolates including transmitted founder viruses is diminished by IFITM3 to various levels, with strain AD8-1 exhibiting strong resistance...
January 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28100610/the-measles-virus-receptor-slamf1-can-mediate-particle-endocytosis
#5
Daniel Gonçalves-Carneiro, Jane A McKeating, Dalan Bailey
: The signalling lymphocyte activation molecule F1 (SLAMF1) is both a microbial sensor and entry receptor for Measles virus (MeV). Herein, we describe a new role for SLAMF1 to mediate MeV endocytosis that is in contrast with the alternative, and generally accepted, model that MeV genome enters cells only after fusion at the cell surface. We demonstrated that MeV engagement of SLAMF1 induces dramatic but transient morphological changes, most prominently in the formation of membrane blebs, which were shown to co-localise with incoming viral particles, and rearrangement of the actin cytoskeleton in infected cells...
January 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28099856/screening-bioactives-reveals-nanchangmycin-as-a-broad-spectrum-antiviral-active-against-zika-virus
#6
Keiko Rausch, Brent A Hackett, Nathan L Weinbren, Sophia M Reeder, Yoel Sadovsky, Christopher A Hunter, David C Schultz, Carolyn B Coyne, Sara Cherry
Zika virus is an emerging arthropod-borne flavivirus for which there are no vaccines or specific therapeutics. We screened a library of 2,000 bioactive compounds for their ability to block Zika virus infection in three distinct cell types with two different strains of Zika virus. Using a microscopy-based assay, we validated 38 drugs that inhibited Zika virus infection, including FDA-approved nucleoside analogs. Cells expressing high levels of the attachment factor AXL can be protected from infection with receptor tyrosine kinase inhibitors, while placental-derived cells that lack AXL expression are insensitive to this inhibition...
January 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/28097165/in-silico-comparison-of-iranian-hiv-1-envelop-glycoprotein-with-five-nearby-countries
#7
Maryam Ghafari, Mandana Behbahani, Hassan Mohabatkar
HIV-1 envelope (env) glycoprotein mediates an important role in entry of the virus into the susceptible target cells. As env glycoprotein of HIV-1 is highly variable in the different geographical regions, in the present study, different properties of this protein in Iran are compared with five nearby countries. The sequences of HIV-1 env glycoproteins of Iran, Afghanistan, Russia, Turkey, Pakistan and Saudi Arabia databases were collected from databases. Amino acid composition and physical and chemical properties of the proteins from these countries were studied using Protparam and COPid tools...
June 2016: Molecular Biology Research Communications
https://www.readbyqxmd.com/read/28097000/biased-small-molecule-ligands-for-selective-inhibition-of-hiv-1-cell-entry-via-ccr5
#8
Christian Berg, Katja Spiess, Hans R Lüttichau, Mette M Rosenkilde
Since the discovery of HIV's use of CCR5 as the primary coreceptor in fusion, the focus on developing small-molecule receptor antagonists for inhibition hereof has only resulted in one single drug, Maraviroc. We therefore investigated the possibility of using small-molecule CCR5 agonists as HIV-1 fusion inhibitors. A virus-free cell-based fusion reporter assay, based on mixing "effector cells" (expressing HIV Env and luciferase activator) with "target cells" (expressing CD4, CCR5 wild type or a selection of well-described mutations, and luciferase reporter), was used as fusion readout...
December 2016: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28090319/the-role-of-liver-sinusoidal-cells-in-local-hepatic-immune-surveillance
#9
REVIEW
Dirk Wohlleber, Percy A Knolle
Although the liver's function as unique immune organ regulating immunity has received a lot of attention over the last years, the mechanisms determining hepatic immune surveillance against infected hepatocytes remain less well defined. Liver sinusoidal cells, in particular, liver sinusoidal endothelial cells (LSECs) and Kupffer cells (KCs), serve as physical platform for recruitment and anchoring of blood-borne immune cells in the liver. Liver sinusoidal cells also function as portal of entry for infectious microorganisms targeting the liver such as hepatotropic viruses, bacteria or parasites...
December 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28081529/zika-virus-induced-microcephaly-and-its-possible-molecular-mechanism
#10
Md Imam Faizan, Mohd Abdullah, Sher Ali, Irshad H Naqvi, Anwar Ahmed, Shama Parveen
Zika virus is an arthropod-borne re-emerging pathogen associated with the global pandemic of 2015-2016. The devastating effect of Zika viral infection is reflected by its neurological manifestations such as microcephaly in newborns. This scenario evoked our interest to uncover the neurotropic localization, multiplication of the virus, and the mechanism of microcephaly. The present report provides an overview of a possible molecular mechanism of Zika virus-induced microcephaly based on recent publications. Transplacental transmission of Zika viral infection from mother to foetus during the first trimester of pregnancy results in propagation of the virus in human neural progenitor cells (hNPCs), where entry is facilitated by the receptor (AXL protein) leading to the alteration of signalling and immune pathways in host cells...
January 13, 2017: Intervirology
https://www.readbyqxmd.com/read/28081264/the-important-role-of-lipid-raft-mediated-attachment-in-the-infection-of-cultured-cells-by-coronavirus-infectious-bronchitis-virus-beaudette-strain
#11
Huichen Guo, Mei Huang, Quan Yuan, Yanquan Wei, Yuan Gao, Lejiao Mao, Lingjun Gu, Yong Wah Tan, Yanxin Zhong, Dingxiang Liu, Shiqi Sun
Lipid raft is an important element for the cellular entry of some viruses, including coronavirus infectious bronchitis virus (IBV). However, the exact role of lipid rafts in the cellular membrane during the entry of IBV into host cells is still unknown. In this study, we biochemically fractionated IBV-infected cells via sucrose density gradient centrifugation after depleting plasma membrane cholesterol with methyl-β-cyclodextrin or Mevastatin. Our results demonstrated that unlike IBV non-structural proteins, IBV structural proteins co-localized with lipid raft marker caveolin-1...
2017: PloS One
https://www.readbyqxmd.com/read/28077878/pla2g16-represents-a-switch-between-entry-and-clearance-of-picornaviridae
#12
Jacqueline Staring, Eleonore von Castelmur, Vincent A Blomen, Lisa G van den Hengel, Markus Brockmann, Jim Baggen, Hendrik Jan Thibaut, Joppe Nieuwenhuis, Hans Janssen, Frank J M van Kuppeveld, Anastassis Perrakis, Jan E Carette, Thijn R Brummelkamp
Picornaviruses are a leading cause of human and veterinary infections that result in various diseases, including polio and the common cold. As archetypical non-enveloped viruses, their biology has been extensively studied. Although a range of different cell-surface receptors are bound by different picornaviruses, it is unclear whether common host factors are needed for them to reach the cytoplasm. Using genome-wide haploid genetic screens, here we identify the lipid-modifying enzyme PLA2G16 (refs 8, 9, 10, 11) as a picornavirus host factor that is required for a previously unknown event in the viral life cycle...
January 19, 2017: Nature
https://www.readbyqxmd.com/read/28077444/protein-interactions-during-the-flavivirus-and-hepacivirus-life-cycle
#13
Gisa Gerold, Janina Bruening, Bettina Weigel, Thomas Pietschmann
Protein-protein interactions govern biological functions in cells, in the extracellular milieu and at the border between cells and extracellular space. Viruses are small intracellular parasites and thus rely on protein interactions to produce progeny inside host cells and to spread from cell to cell. Usage of host proteins by viruses can have severe consequences e.g. apoptosis, metabolic disequilibria or altered cell proliferation and mobility. Understanding protein interactions during virus infection can thus educate us on viral infection and pathogenesis mechanisms...
January 11, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28076788/dynamin-2-stabilizes-the-hiv-1-fusion-pore-with-a-low-oligomeric-state
#14
Daniel M Jones, Luis A Alvarez, Rory Nolan, Margarita Ferriz, Raquel Sainz Urruela, Xènia Massana-Muñoz, Hila Novak-Kotzer, Michael L Dustin, Sergi Padilla-Parra
One of the key research areas surrounding HIV-1 concerns the regulation of the fusion event that occurs between the virus particle and the host cell during entry. Even if it is universally accepted that the large GTPase dynamin-2 is important during HIV-1 entry, its exact role during the first steps of HIV-1 infection is not well characterized. Here, we have utilized a multidisciplinary approach to study the DNM2 role during fusion of HIV-1 in primary resting CD4 T and TZM-bl cells. We have combined advanced light microscopy and functional cell-based assays to experimentally assess the role of dynamin-2 during these processes...
January 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28076778/axl-mediates-zika-virus-entry-in-human-glial-cells-and-modulates-innate-immune-responses
#15
Laurent Meertens, Athena Labeau, Ophelie Dejarnac, Sara Cipriani, Laura Sinigaglia, Lucie Bonnet-Madin, Tifenn Le Charpentier, Mohamed Lamine Hafirassou, Alessia Zamborlini, Van-Mai Cao-Lormeau, Muriel Coulpier, Dorothée Missé, Nolwenn Jouvenet, Ray Tabibiazar, Pierre Gressens, Olivier Schwartz, Ali Amara
ZIKA virus (ZIKV) is an emerging pathogen responsible for neurological disorders and congenital microcephaly. However, the molecular basis for ZIKV neurotropism remains poorly understood. Here, we show that Axl is expressed in human microglia and astrocytes in the developing brain and that it mediates ZIKV infection of glial cells. Axl-mediated ZIKV entry requires the Axl ligand Gas6, which bridges ZIKV particles to glial cells. Following binding, ZIKV is internalized through clathrin-mediated endocytosis and traffics to Rab5+ endosomes to establish productive infection...
January 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28076686/small-molecule-hiv-1-entry-inhibitors-targeting-gp120-and-gp41-a-patent-review-2010-2015
#16
Wen Li, Lu Lu, Weihua Li, Shibo Jiang
It is essential to discover and develop small-molecule HIV-1 entry inhibitors with suitable pharmaceutical properties. Areas covered: We review the development of small-molecule HIV-1 entry inhibitors as evidenced in patents, patent applications, and related research articles published between 2010 and 2015. Expert opinion: HIV-1 Env gp120 and gp41 are important targets for development of HIV-1 entry inhibitors. The Phe43 pocket in gp120 and the highly conserved hydrophobic pocket on gp41 NHR-trimer are important targets for identification of HIV-1 attachment and fusion inhibitors, respectively...
January 19, 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/28073681/association-of-cytoplasmic-cxcr4-with-loss-of-epithelial-marker-and-activation-of-erk1-2-and-akt-signaling-pathways-in-non-small-cell-lung%C3%A2-cancer
#17
Nabil F Saba, Yuxiang Wang, Hongpeng Fu, Lydia Koenig, Fadlo R Khuri, Dong M Shin, Zhuo Georgia Chen
OBJECTIVES: Compelling evidence demonstrates that CXC-chemokine receptor 4 (CXCR4) is involved in tumor invasion, angiogenesis, metastasis, and resistance to chemotherapy in addition to being one of the coreceptors for T-tropic human immunodeficiency virus entry into T cells. However, it remains controversial as to how to identify functionally activated CXCR4 in tumor biopsies, which would assist in determining which patients may benefit from potential CXCR4-targeted therapy. MATERIALS AND METHODS: Immunohistochemistry (IHC) staining on archival tissues of patients with non-small-cell lung cancer (NSCLC) was used to detect a panel of biomarkers, including phospho-ERK1/2, phospho-AKT, and E-cadherin, which are relevant to downstream signaling of CXCR4 and epithelial to mesenchymal transition (EMT)...
December 22, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28069361/dna-mva-protein-vaccination-of-rhesus-macaques-induces-hiv-specific-immunity-in-mucosal-associated-lymph-nodes-and-functional-antibodies
#18
Gerald K Chege, Wendy A Burgers, Tracey L Müller, Clive M Gray, Enid G Shephard, Susan W Barnett, Guido Ferrari, David Montefiori, Carolyn Williamson, Anna-Lise Williamson
Successful future HIV vaccines are expected to generate an effective cellular and humoral response against the virus in both the peripheral blood and mucosal compartments. We previously reported the development of DNA-C and MVA-C vaccines based on HIV-1 subtype C and demonstrated their immunogenicity when given in a DNA prime-MVA boost combination in a nonhuman primate model. In the current study, rhesus macaques previously vaccinated with a DNA-C and MVA-C vaccine regimen were re-vaccinated 3.5years later with MVA-C followed by a protein vaccine based on HIV-1 subtype C envelope formulated with MF59 adjuvant (gp140Env/MF59), and finally a concurrent boost with both vaccines...
January 6, 2017: Vaccine
https://www.readbyqxmd.com/read/28065506/cryoelectron-microscopy-maps-of-human-papillomavirus-16-reveal-l2-densities-and-heparin-binding-site
#19
Jian Guan, Stephanie M Bywaters, Sarah A Brendle, Robert E Ashley, Alexander M Makhov, James F Conway, Neil D Christensen, Susan Hafenstein
Human papillomavirus (HPV) is a significant health burden and leading cause of virus-induced cancers. The current commercial vaccines are genotype specific and provide little therapeutic benefit to patients with existing HPV infections. Host entry mechanisms represent an excellent target for alternative therapeutics, but HPV receptor use, the details of cell attachment, and host entry are inadequately understood. Here we present near-atomic resolution structures of the HPV16 capsid and HPV16 in complex with heparin, both determined from cryoelectron micrographs collected with direct electron detection technology...
December 31, 2016: Structure
https://www.readbyqxmd.com/read/28062010/splenic-cd163-macrophages-as-targets-of-porcine-reproductive-and-respiratory-virus-role-of-siglecs
#20
María Yuste, Teresa Fernández-Caballero, Cinta Prieto, Belén Álvarez, Javier Martínez-Lobo, Isabel Simarro, José María Castro, Fernando Alonso, Ángel Ezquerra, Javier Domínguez, Concepción Revilla
CD169 and CD163 have been involved in the process of PRRS virus attachment and infection in macrophages, although recent studies have challenged the requirement for CD169. In addition to CD169, macrophages express other siglecs, whose role in PRRS virus infection is so far unknown. Splenic CD163(+) macrophages express Siglec-3 and Siglec-5 but almost undetectable levels of CD169. Hence, we considered this cell population appropriate for analysing the role of these siglecs in the attachment and internalization of PRRS virus into macrophages...
January 2017: Veterinary Microbiology
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