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Shigetaka Yoneda, Yukina Hara-Yamada, Aya Kosugi, Maiko Nanao, Takami Saito, Shunsuke Sato, Nozomu Yamada, Go Watanabe
A new program library named "CAPLIB" was developed for the modeling and analysis of icosahedrally symmetric virus capsids. CAPLIB is equipped with the mathematical data of 60 rotation matrices of icosahedral symmetry, 15 planes bisecting the entire capsid structure, and a table summarizing how the 60 asymmetric units (cells) are partitioned by the planes. CAPLIB contains the function to determine the cell numbers of atoms from the atomic positions and the function to determine the rotation axes and angles from the rotation matrices...
April 30, 2018: ACS Omega
Laura Sinigaglia, Ségolène Gracias, Elodie Décembre, Matthieu Fritz, Daniela Bruni, Nikaïa Smith, Jean-Philippe Herbeuval, Annette Martin, Marlène Dreux, Frédéric Tangy, Nolwenn Jouvenet
Plasmacytoid dendritic cells (pDCs) are specialized in the production of interferons (IFNs) in response to viral infections. The Flaviviridae family comprises enveloped RNA viruses such as Hepatitis C virus (HCV) and Dengue virus (DENV). Cell-free flaviviridae virions poorly stimulate pDCs to produce IFN. By contrast, cells infected with HCV and DENV potently stimulate pDCs via short-range delivery of viral RNAs, which are either packaged within immature virions or secreted exosomes. We report that cells infected with Yellow fever virus (YFV), the prototypical flavivirus, stimulated pDCs to produce IFNs in a TLR7- and cell contact- dependent manner...
July 18, 2018: Scientific Reports
Dafni Chondronasiou, Tracy-Jane T H D Eisden, Anita G M Stam, Qiana L Matthews, Mert Icyuz, Erik Hooijberg, Igor Dmitriev, David T Curiel, Tanja D de Gruijl, Rieneke van de Ven
To mount a strong anti-tumor immune response, non T cell inflamed (cold) tumors may require combination treatment encompassing vaccine strategies preceding checkpoint inhibition. In vivo targeted delivery of tumor-associated antigens (TAA) to dendritic cells (DCs), relying on the natural functions of primary DCs in situ, represents an attractive vaccination strategy. In this study we made use of a full-length MART-1 expressing C/B-chimeric adenoviral vector, consisting of the Ad5 capsid and the Ad3 knob (Ad5/3), which we previously showed to selectively transduce DCs in human skin and lymph nodes...
July 18, 2018: Vaccines
Carlos P Mata, Johann Mertens, Juan Fontana, Daniel Luque, Carolina Allende-Ballestero, David Reguera, Benes L Trus, Alasdair C Steven, José L Carrascosa, José R Castón
Infectious bursal disease virus (IBDV), a non-enveloped, double-stranded (ds)RNA virus with a T=13 icosahedral capsid, has a virion assembly strategy that initiates with a precursor particle based on an internal scaffold shell similar to that of tailed dsDNA viruses. In IBDV-infected cells, the assembly pathway results mainly in mature virions that package four dsRNA segments, although minor viral populations ranging from zero to three dsRNA segments also form. We used cryo-electron microscopy, cryo-electron tomography and atomic force microscopy to characterize these IBDV populations...
July 18, 2018: Journal of Virology
Elena Wüstenhagen, Fatima Boukhallouk, Inka Negwer, Krishnaraj Rajalingam, Frank Stubenrauch, Luise Florin
The skin represents a physical and chemical barrier against invading pathogens, which is additionally supported by restriction factors that provide intrinsic cellular immunity. These factors detect viruses to block their replication cycle. Here, we uncover the Myb-related transcription factor, partner of profilin (MYPOP) as a novel antiviral protein. It is highly expressed in the epithelium and binds to the minor capsid protein L2 and the DNA of human papillomaviruses (HPV), which are the primary causative agents of cervical cancer and other tumors...
July 17, 2018: Oncogene
Agnieszka Figas, Magdalena Wieczorek, Anna Żuk-Wasek, Bogumiła Litwińska
As a complement to the active search for cases of acute flaccid paralysis, environmental sampling was conducted from January to December 2011, to test for any putative polio revertants and recombinants in sewage. A total of 165 environmental samples were obtained and analyzed for the presence of polioviruses by use of cell culture (L20B, RD and Caco-2) followed by neutralization and reverse-transcription polymerase chain reaction. Out of the 31 CPE positive samples, 26 contained one and 5 two different serotypes, yielding a total of 36 PVs...
March 9, 2018: Polish Journal of Microbiology
Thomas Lahlali, Jan Martin Berke, Karen Vergauwen, Adrien Foca, Koen Vandyck, Frederik Pauwels, Fabien Zoulim, David Durantel
The assembly of hepatitis B virus (HBV) core proteins (HBc) into capsids represents a critical step of viral replication. HBc has multiple functions during the HBV life cycle, which makes it an attractive target for antiviral therapies. Capsid assembly modulators (CAMs) induce the formation of empty-capsid or aberrant-capsid devoid of pregenomic RNA (pgRNA) and finally block rcDNA neosynthesis and virion progeny. In this study, novel CAMs JNJ-827 and JNJ-890, were found to be potent inhibitors of HBV replication with a respective half maximal effective concentration of 4...
July 16, 2018: Antimicrobial Agents and Chemotherapy
Evgeny N Kozlov, Elena U Martynova, Vladimir I Popenko, Coby Schal, Dmitry V Mukha
Densovirus genome replication and capsid assembly take place in the nucleus of the infected cells. However, the mechanisms underlying such processes as the delivery of virus proteins to the nucleus and the export of progeny virus from the nucleus remain elusive. It is evident that nuclear transport signals should be involved in these processes. We performed an in silico search for the putative nuclear localization signal (NLS) and nuclear export signal (NES) motifs in the capsid proteins of the Blattella germanica Densovirus 1 (BgDV1) densovirus...
July 14, 2018: Viruses
Kannan Badri Narayanan, Sung Soo Han
Plant virus-based nanoparticles (PVNs) are self-assembled capsid proteins of plant viruses, and can be virus-like nanoparticles (VLPs) or virus nanoparticles (VNPs). Plant viruses showing helical capsid symmetry are used as a versatile platform for the presentation of multiple copies of well-arrayed immunogenic antigens of various disease pathogens. Helical PVNs are non-infectious, biocompatible, and naturally immunogenic, and thus, they are suitable antigen carriers for vaccine production and can trigger humoral and/or cellular immune responses...
July 14, 2018: Virus Genes
Takamasa Inoue, Pengwei Zhang, Wei Zhang, Kylia Goodner-Bingham, Allison Dupzyk, Daniel DiMaio, Billy Tsai
Despite their importance as human pathogens, entry of human papillomaviruses (HPVs) into cells is poorly understood. The transmembrane protease γ-secretase executes a crucial function during the early stages of HPV infection, but the role of γ-secretase in infection and the identity of its critical substrate are unknown. Here we demonstrate that γ-secretase harbors a previously uncharacterized chaperone function, promoting low pH-dependent insertion of the HPV L2 capsid protein into endosomal membranes. Upon membrane insertion, L2 recruits the cytosolic retromer, which enables the L2 viral genome complex to enter the retrograde transport pathway and traffic to the Golgi en route for infection...
July 13, 2018: Journal of Cell Biology
Mona O Mohsen, Ariane C Gomes, Monique Vogel, Martin F Bachmann
Virus-like particles (VLPs) derived from viral nucleocapsids are an important class of nanoparticles. The structure, uniformity, stability, and function of these VLPs have attracted scientists in utilizing them as a unique tool in various applications in biomedical fields. Their interaction with the innate immune system is of major importance for the adaptive immune response they induce. The innate immune cells and molecules recognize and interact with VLPs on the basis of two major characteristics: size and surface geometry...
July 2, 2018: Vaccines
Su-Kyung Lee, Seoheui Choi, Seon-Hee Shin, Eun Jin Lee, Jungwon Hyun, Jae-Seok Kim, Hyun Soo Kim
Background: Rotaviruses are the major causes of pediatric gastroenteritis worldwide. The genotypic distribution of rotavirus strains shows temporal and geographical fluctuations, and knowledge of the molecular epidemiology of rotaviruses is important for the development of vaccines and diagnostic reagents. We investigated VP4 and VP7 capsid genotypes of rotaviruses isolated from 211 stool specimens collected from Korean neonates in a neonatal intensive care unit from September 2017 to March 2018...
2018: Gut Pathogens
Qiang Zheng, Qi Chen, Yongle Xu, Curtis A Suttle, Nianzhi Jiao
In recent metagenomic studies, single-stranded DNA (ssDNA) viruses that infect bacteria have been shown to be diverse and prevalent in the ocean; however, there are few isolates of marine ssDNA phages. Here, we report on a cultivated ssDNA phage (vB_Cib_ssDNA_P1) that infects Citromicrobium bathyomarinum RCC1878 (family Sphingomonadaceae ), and other members of the genus. This is the first ssDNA phage reported to infect marine alphaproteobacteria, and represents a newly recognized lineage of the Microviridae infecting members of Sphingomonadaceae , the Amoyvirinae ...
2018: Frontiers in Microbiology
Cindy Buffone, Alicia Martinez-Lopez, Thomas Fricke, Silvana Opp, Marco Severgnini, Ingrid Cifola, Luca Petiti, Stella Frabetti, Katarzyna Skorupka, Kaneil K Zadrozny, Barbie K Ganser-Pornillos, Owen Pornillos, Francesca Di Nunzio, Felipe Diaz-Griffero
HIV-1 displays the unique ability to infect non-dividing cells. The capsid of HIV-1 is the viral determinant for viral nuclear import. To understand the cellular factors involved in the ability of HIV-1 to infect non-dividing cells, we sought to find capsid mutations that allow the virus to infect dividing but not non-dividing cells. Because the interaction of capsid with the nucleoporin protein 153 (Nup153) is important for nuclear import of HIV-1, we solved new crystal structures of hexameric HIV-1 capsid in complex with a Nup153-derived peptide containing a phenylalanine-glycine repeat (FG-repeat), which we used to guide structure-based mutagenesis of the capsid-binding interface...
July 11, 2018: Journal of Virology
Natalia Sierra, Christelle Folio, Xavier Robert, Mathieu Long, Christophe Guillon, Guzmán Álvarez
Feline immunodeficiency virus (FIV) is a member of the retroviridae family of viruses. It causes acquired immunodeficiency syndrome (AIDS) in worldwide domestic and non-domestic cats and is a cause of an important veterinary issue. The genome organization of FIV and the clinical characteristics of the disease caused by FIV are similar to human immunodeficiency virus (HIV). Both viruses infect T lymphocytes, monocytes, and macrophages, with a similar replication cycle in infected cells. Thus, the infection of cats with FIV is also a useful tool for the study and development of novel drugs and vaccines against HIV...
July 10, 2018: Pharmaceuticals
Guibo Rao, Yan Fu, Na Li, Jiayi Yin, Jie Zhang, Manli Wang, Zhihong Hu, Sheng Cao
Viruses with filamentous morphologies, such as tobacco mosaic virus (TMV) and M13 bacteriophage, have long been studied as multivalent nano-scaffolds for loading functional motifs. Structural assembly of the capsid proteins (CPs) of filamentous viruses often requires the presence of DNA or RNA molecules, which has limited their applications. Here, we describe a strategy for controllable assembly of flexible bio-nanotubes consisting of Escherichia coli expressed CP of baculovirus Helicoverpa armigera nucleopolyhedrovirus (HearNPV) in vitro...
July 10, 2018: ACS Applied Materials & Interfaces
Michaela Procházková, Tibor Füzik, Karel Škubník, Jana Moravcová, Zorica Ubiparip, Antonín Přidal, Pavel Plevka
Infection by sacbrood virus (SBV) from the family Iflaviridae is lethal to honey bee larvae but only rarely causes the collapse of honey bee colonies. Despite the negative effect of SBV on honey bees, the structure of its particles and mechanism of its genome delivery are unknown. Here we present the crystal structure of SBV virion and show that it contains 60 copies of a minor capsid protein (MiCP) attached to the virion surface. No similar MiCPs have been previously reported in any of the related viruses from the order Picornavirales...
July 9, 2018: Proceedings of the National Academy of Sciences of the United States of America
Rafhaella D G Gondim, Rafaela C Pankov, Mara M G Prata, Pedro H Q S Medeiros, Herlice N Veras, Ana K S Santos, Lyvia M C Magalhães, Alexandre Havt, Tulio M Fumian, Marize P Miagostovich, José P G Leite, Aldo A M Lima
BACKGROUND: Norovirus (NoV) infections are known to have high morbidity and mortality rates and are a major health problem globally. However, the impact of NoV on child development is poorly understood. OBJECTIVE: We evaluated the distribution of NoV genotypes in children from a low-income Brazilian semiarid region, in relation with their clinical symptoms, nutritional status, and co-pathogens. METHODS: The test population included children aged 2-36 months from six cities of the Brazilian semiarid region...
July 6, 2018: Journal of Pediatric Gastroenterology and Nutrition
Elena Senís, Lluc Mosteiro, Stefan Wilkening, Ellen Wiedtke, Ali Nowrouzi, Saira Afzal, Raffaele Fronza, Henrik Landerer, Maria Abad, Dominik Niopek, Manfred Schmidt, Manuel Serrano, Dirk Grimm
In vivo reprogramming of somatic cells into induced pluripotent stem cells (iPSC) holds vast potential for basic research and regenerative medicine. However, it remains hampered by a need for vectors to express reprogramming factors (Oct-3/4, Klf4, Sox2, c-Myc; OKSM) in selected organs. Here, we report OKSM delivery vectors based on pseudotyped Adeno-associated virus (AAV). Using the AAV-DJ capsid, we could robustly reprogram mouse embryonic fibroblasts with low vector doses. Swapping to AAV8 permitted to efficiently reprogram somatic cells in adult mice by intravenous vector delivery, evidenced by hepatic or extra-hepatic teratomas and iPSC in the blood...
July 9, 2018: Nature Communications
John M Powers, Xiao Lan Chang, Zhen Song, Hiroyuki Nakai
While adeno-associated virus (AAV) is widely accepted as an attractive vector for gene therapy, it also serves as a model virus for understanding virus biology. In the latter respect, the recent discovery of a non-structural AAV protein, termed assembly-activating protein (AAP), has shed new light on the processes involved in assembly of the viral capsid VP proteins into a capsid. Although many AAV serotypes require AAP for assembly, we have recently reported that AAV4, 5, and 11 are exceptions to this rule...
June 12, 2018: Journal of Visualized Experiments: JoVE
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