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https://www.readbyqxmd.com/read/28346537/deep-mutational-scanning-identifies-sites-in-influenza-nucleoprotein-that-affect-viral-inhibition-by-mxa
#1
Orr Ashenberg, Jai Padmakumar, Michael B Doud, Jesse D Bloom
The innate-immune restriction factor MxA inhibits influenza replication by targeting the viral nucleoprotein (NP). Human influenza virus is more resistant than avian influenza virus to inhibition by human MxA, and prior work has compared human and avian viral strains to identify amino-acid differences in NP that affect sensitivity to MxA. However, this strategy is limited to identifying sites in NP where mutations that affect MxA sensitivity have fixed during the small number of documented zoonotic transmissions of influenza to humans...
March 27, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28346455/collective-helicity-switching-of-a-dna-coat-assembly
#2
Yongju Kim, Huichang Li, Ying He, Xi Chen, Xiaoteng Ma, Myongsoo Lee
Hierarchical assemblies of biomolecular subunits can carry out versatile tasks at the cellular level with remarkable spatial and temporal precision. As an example, the collective motion and mutual cooperation between complex protein machines mediate essential functions for life, such as replication, synthesis, degradation, repair and transport. Nucleic acid molecules are far less dynamic than proteins and need to bind to specific proteins to form hierarchical structures. The simplest example of these nucleic acid-based structures is provided by a rod-shaped tobacco mosaic virus, which consists of genetic material surrounded by coat proteins...
March 27, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/28346446/dengue-virus-ns2b-protein-targets-cgas-for-degradation-and-prevents-mitochondrial-dna-sensing-during-infection
#3
Sebastian Aguirre, Priya Luthra, Maria T Sanchez-Aparicio, Ana M Maestre, Jenish Patel, Francise Lamothe, Anthony C Fredericks, Shashank Tripathi, Tongtong Zhu, Jessica Pintado-Silva, Laurence G Webb, Dabeiba Bernal-Rubio, Alexander Solovyov, Benjamin Greenbaum, Viviana Simon, Christopher F Basler, Lubbertus C F Mulder, Adolfo García-Sastre, Ana Fernandez-Sesma
During the last few decades, the global incidence of dengue virus (DENV) has increased dramatically, and it is now endemic in more than 100 countries. To establish a productive infection in humans, DENV uses different strategies to inhibit or avoid the host innate immune system. Several DENV proteins have been shown to strategically target crucial components of the type I interferon system. Here, we report that the DENV NS2B protease cofactor targets the DNA sensor cyclic GMP-AMP synthase (cGAS) for lysosomal degradation to avoid the detection of mitochondrial DNA during infection...
March 27, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28346011/various-plus-unique-viral-protein-u-as-a-plurifunctional-protein-for-hiv-1-replication
#4
Andrew Soper, Guillermo Juarez-Fernandez, Hirofumi Aso, Miyu Moriwaki, Eri Yamada, Yusuke Nakano, Yoshio Koyanagi, Kei Sato
Human immunodeficiency virus type 1 (HIV-1), the causative agent of acquired immunodeficiency syndrome, encodes four accessory genes, one of which is viral protein U (Vpu). Recently, the study of Vpu has been of great interest. For instance, various cellular proteins are degraded (e.g. CD4) and down-modulated (e.g. tetherin) by Vpu. Vpu also antagonizes the function of tetherin and inhibits NF-κB. Moreover, Vpu is a viroporin forming ion channels and may represent a promising target for anti-HIV-1 drugs. In this review, we summarize the domains/residues that are responsible for Vpu's functions, describe the current understanding of the role of Vpu in HIV-1-infected cells, and review the effect of Vpu on HIV-1 in replication and pathogenesis...
April 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28345874/delivery-of-pesticides-to-plant-parasitic-nematodes-using-tobacco-mild-green-mosaic-virus-as-a-nanocarrier
#5
Paul L Chariou, Nicole F Steinmetz
Plant parasitic nematodes are a major burden to the global agricultural industry, causing a $157 billion loss each year in crop production worldwide. Effective treatment requires large doses of nematicides to be applied, putting the environment and human health at risk. Challenges are to treat nematodes that are located deep within the soil, feeding on the roots of plants. To attack the problem at its roots, we propose the use of tobacco mild green mosaic virus (TMGMV), an EPA-approved herbicide as a carrier to deliver nematicides...
March 27, 2017: ACS Nano
https://www.readbyqxmd.com/read/28345819/outbreak-investigations-and-molecular-characterization-of-foot-and-mouth-disease-viruses-circulating-in-south-west-niger
#6
B Souley Kouato, F M Elliot, D P King, J Hyera, N J Knowles, A B Ludi, V Mioulet, G Matlho, K De Clercq, E Thys, H Marichatou, S Issa, C Saegerman
In Niger, the epidemiological situation regarding foot-and-mouth disease is unclear as many outbreaks are unreported. This study aimed (i) to identify Foot-and-mouth disease virus (FMDV) strains currently circulating in cattle herds, and (ii) to identify risk factors associated with Foot-and-mouth disease (FMD)-seropositive animals in clinical outbreaks. Epithelial tissues (n = 25) and sera (n = 227) were collected from cattle in eight districts of the south-western part of Niger. Testing of clinical material revealed the presence of FMDV serotype O that was characterized within the O/WEST AFRICA topotype...
March 27, 2017: Transboundary and Emerging Diseases
https://www.readbyqxmd.com/read/28345656/structure-and-function-of-the-zika-virus-full-length-ns5-protein
#7
Baoyu Zhao, Guanghui Yi, Fenglei Du, Yin-Chih Chuang, Robert C Vaughan, Banumathi Sankaran, C Cheng Kao, Pingwei Li
The recent outbreak of Zika virus (ZIKV) has infected over 1 million people in over 30 countries. ZIKV replicates its RNA genome using virally encoded replication proteins. Nonstructural protein 5 (NS5) contains a methyltransferase for RNA capping and a polymerase for viral RNA synthesis. Here we report the crystal structures of full-length NS5 and its polymerase domain at 3.0 Å resolution. The NS5 structure has striking similarities to the NS5 protein of the related Japanese encephalitis virus. The methyltransferase contains in-line pockets for substrate binding and the active site...
March 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28345603/pja2-ubiquitinates-the-hiv-1-tat-protein-with-atypical-chain-linkages-to-activate-viral-transcription
#8
Tyler B Faust, Yang Li, Gwendolyn M Jang, Jeffrey R Johnson, Shumin Yang, Amit Weiss, Nevan J Krogan, Alan D Frankel
Transcription complexes that assemble at the HIV-1 promoter efficiently initiate transcription but generate paused RNA polymerase II downstream from the start site. The virally encoded Tat protein hijacks positive transcription elongation factor b (P-TEFb) to phosphorylate and activate this paused polymerase. In addition, Tat undergoes a series of reversible post-translational modifications that regulate distinct steps of the transcription cycle. To identify additional functionally important Tat cofactors, we performed RNAi knockdowns of sixteen previously identified Tat interactors and found that a novel E3 ligase, PJA2, ubiquitinates Tat in a non-degradative manner and specifically regulates the step of HIV transcription elongation...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28345600/the-structure-of-zika-virus-ns5-reveals-a-conserved-domain-conformation
#9
Boxiao Wang, Xiao-Feng Tan, Stephanie Thurmond, Zhi-Min Zhang, Asher Lin, Rong Hai, Jikui Song
The recent outbreak of Zika virus (ZIKV) has imposed a serious threat to public health. Here we report the crystal structure of the ZIKV NS5 protein in complex with S-adenosyl-L-homocysteine, in which the tandem methyltransferase (MTase) and RNA-dependent RNA polymerase (RdRp) domains stack into one of the two alternative conformations of flavivirus NS5 proteins. The activity of this NS5 protein is verified through a de novo RdRp assay on a subgenomic ZIKV RNA template. Importantly, our structural analysis leads to the identification of a potential drug-binding site of ZIKV NS5, which might facilitate the development of novel antivirals for ZIKV...
March 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28345596/crystal-structure-of-zika-virus-ns5-rna-dependent-rna-polymerase
#10
Andre S Godoy, Gustavo M A Lima, Ketllyn I Z Oliveira, Naiara U Torres, Fernando V Maluf, Rafael V C Guido, Glaucius Oliva
The current Zika virus (ZIKV) outbreak became a global health threat of complex epidemiology and devastating neurological impacts, therefore requiring urgent efforts towards the development of novel efficacious and safe antiviral drugs. Due to its central role in RNA viral replication, the non-structural protein 5 (NS5) RNA-dependent RNA-polymerase (RdRp) is a prime target for drug discovery. Here we describe the crystal structure of the recombinant ZIKV NS5 RdRp domain at 1.9 Å resolution as a platform for structure-based drug design strategy...
March 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28345552/relationship-between-hepatitis-c-virus-infection-and-iron-overload
#11
REVIEW
Dong-Mei Zou, Wan-Ling Sun
OBJECTIVE: The aim of this study was to summarize the interactions between hepatitis C virus (HCV) infection and iron overload, and to understand the mechanisms of iron overload in chronic hepatitis C (CHC) and the role iron plays in HCV life cycle. DATA SOURCES: This review was based on data in articles published in the PubMed databases up to January 28, 2017, with the keywords "hepatitis C virus", "iron overload", "iron metabolism", "hepcidin", "translation", and "replication"...
April 5, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28345428/induction-of-t-cell-infiltration-and-programmed-death-ligand-2-expression-by-adeno-associated-virus-in-rhesus-macaque-skeletal-muscle-and-modulation-by-prednisone
#12
Megan L Cramer, Guohong Shao, Louise R Rodino-Klapac, Louis G Chicoine, Paul T Martin
Use of adeno-associated virus (AAV) to transduce genes into skeletal muscles can be associated with T-cell responses to viral capsid and/or to transgenic protein. Intramuscular mononuclear cell infiltrates primarily consisting of CD8+ T cells and also containing FOXP3+ regulatory T cells were present in rhesus macaque skeletal muscle treated with rAAVrh74.MCK.GALGT2 by vascular delivery. Administration of oral prednisone prior to AAV gene delivery and throughout the study reduced such infiltrates by 60% at 24 weeks post-AAV delivery compared to AAV-treated animals not receiving prednisone, regardless of the presence of pre-existing AAV serum antibodies at the time of treatment...
March 27, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28345325/potential-role-of-e4-protein-in-human-papillomavirus-screening-a-review
#13
REVIEW
Aidy Irman Yajid, Mohd Azali Zakariah, Anani Aila Mat Zin, Nor Hayati Othman
In 2006, cervical cancer was reported as the second most common cancer in women of Malaysia. This type of cancer has been shown to correlate with persistent high risk human papillomavirus (HPV) infection. Although HPV is well known to induce cervical cancer, knowledge of pathways that link the latent stage of the viral replication cycle to precancerous and cancerous stages remains incomplete. However, it is interesting to note that the virus can be isolated from tissues ranging from normal to low-grade squamous intraepithelial lesions as well as high-grade intraepithelial lesions (HSILs), thus prompting scientists to develop HPV detection methods for screening...
February 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28344997/simple-derivation-of-spinal-motor-neurons-from-escs-ipscs-using-sendai-virus-vectors
#14
Kazuya Goto, Keiko Imamura, Kenichi Komatsu, Kohnosuke Mitani, Kazuhiro Aiba, Norio Nakatsuji, Makoto Inoue, Akihiro Kawata, Hirofumi Yamashita, Ryosuke Takahashi, Haruhisa Inoue
Amyotrophic lateral sclerosis (ALS) is a progressive and fatal degenerative disorder of motor neurons (MNs). Embryonic stem cells (ESCs)/induced pluripotent stem cells (iPSCs) now help us to understand the pathomechanisms of ALS via disease modeling. Various methods to differentiate ESCs/iPSCs into MNs by the addition of signaling molecules have been reported. However, classical methods require multiple steps, and newer simple methods using the transduction of transcription factors run the risk of genomic integration of the vector genes...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28344876/2b4-sap-signaling-is-required-for-the-priming-of-naive-cd8-t-cells-by-antigen-expressing-b-cells-and-b-lymphoma-cells
#15
Yu-Hsuan Huang, Kevin Tsai, Sara Y Tan, Sohyeong Kang, Mandy L Ford, Kenneth W Harder, John J Priatel
Mutations in SH2D1A gene that encodes SAP (SLAM-associated protein) result in X-linked lymphoproliferative disease (XLP), a rare primary immunodeficiency disease defined by exquisite sensitivity to the B-lymphotropic Epstein-Barr virus (EBV) and B cell lymphomas. However, the precise mechanism of how the loss of SAP function contributes to extreme vulnerability to EBV and the development of B cell lymphomas remains unclear. Here, we investigate the hypothesis that SAP is critical for CD8(+) T cell immune surveillance of antigen (Ag)-expressing B cells or B lymphoma cells under conditions of defined T cell receptor (TCR) signaling...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344867/cd4-and-cd8-t-cells-are-both-needed-to-induce-paraneoplastic-neurological-disease-in-a-mouse-model
#16
Christina Gebauer, Béatrice Pignolet, Lidia Yshii, Emilie Mauré, Jan Bauer, Roland Liblau
Paraneoplastic neurological disorders (PNDs) are rare human autoimmune diseases that mostly affect the central nervous system (CNS). They are triggered by an efficient immune response against a neural self-antigen that is ectopically expressed in neoplastic tumors. Due to this shared antigenic expression, the immune system reacts not only to tumor cells but also to neural cells resulting in neurological damage. Growing data point to a major role of cell-mediated immunity in PNDs associated to autoantibodies against intracellular proteins...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344581/type-i-interferons-as-regulators-of-lung-inflammation
#17
REVIEW
Spyridon Makris, Michelle Paulsen, Cecilia Johansson
Immune responses to lung infections must be tightly regulated in order to permit pathogen eradication while maintaining organ function. Exuberant or dysregulated inflammation can impair gas exchange and underlies many instances of lung disease. An important driver of inflammation in the lung is the interferon (IFN) response. Type I IFNs are antiviral cytokines that induce a large range of proteins that impair viral replication in infected cells. This cell-intrinsic action plays a crucial role in protecting the lungs from spread of respiratory viruses...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28344576/genomic-characterization-of-recent-chicken-anemia-virus-isolates-in-china
#18
Yang Li, Lichun Fang, Shuai Cui, Jiayuan Fu, Xiaohan Li, Huanmin Zhang, Zhizhong Cui, Shuang Chang, Weifeng Shi, Peng Zhao
Chicken anemia virus (CAV) causes diseases in young chickens, which include increased pathogenicity of secondary infectious agents, generalized lymphoid depletion, and immunodepression. In the present study, we have identified 22 CAV strains isolated from several commercial chicken farms in Northern China during 2014-2015. In addition, two CAVs were also isolated from stray mouse and dog feces, respectively. To our knowledge, this is the first report of identification of CAV from mouse and dog feces. Phylogenetic analysis of 121 full-length CAV genome sequences showed that all available CAV could be classified into eight lineages, supported by phylogenetic trees estimated using different methods...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28344575/identification-of-capsid-coat-related-protein-folds-and-their-utility-for-virus-classification
#19
Arshan Nasir, Gustavo Caetano-Anollés
The viral supergroup includes the entire collection of known and unknown viruses that roam our planet and infect life forms. The supergroup is remarkably diverse both in its genetics and morphology and has historically remained difficult to study and classify. The accumulation of protein structure data in the past few years now provides an excellent opportunity to re-examine the classification and evolution of viruses. Here we scan completely sequenced viral proteomes from all genome types and identify protein folds involved in the formation of viral capsids and virion architectures...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28344571/translation-initiation-factor-eif4e-and-eifiso4e-are-both-required-for-peanut-stripe-virus-infection-in-peanut-arachis-hypogaea-l
#20
Manlin Xu, Hongfeng Xie, Juxiang Wu, Lianhui Xie, Jinguang Yang, Yucheng Chi
Peanut stripe virus (PStV) belongs to the genus Potyvirus and is the most important viral pathogen of cultivated peanut (Arachis hypogaea L.). The eukaryotic translation initiation factor, eIF4E, and its isoform, eIF(iso)4E, play key roles during virus infection in plants, particularly Potyvirus. In the present study, we cloned the eIF4E and eIF(iso)4E homologs in peanut and named these as PeaeIF4E and PeaeIF(iso)4E, respectively. Quantitative real-time PCR (qRT-PCR) analysis showed that these two genes were expressed during all growth periods and in all peanut organs, but were especially abundant in young leaves and roots...
2017: Frontiers in Microbiology
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