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https://www.readbyqxmd.com/read/28930676/localized-phosphorylation-of-a-kinesin-1-adaptor-by-a-capsid-associated-kinase-regulates-hiv-1-motility-and-uncoating
#1
Viacheslav Malikov, Mojgan H Naghavi
Although microtubule motors mediate intracellular virus transport, the underlying interactions and control mechanisms remain poorly defined. This is particularly true for HIV-1 cores, which undergo complex, interconnected processes of cytosolic transport, reverse transcription, and uncoating of the capsid shell. Although kinesins have been implicated in regulating these events, curiously, there are no direct kinesin-core interactions. We recently showed that the capsid-associated kinesin-1 adaptor protein, fasciculation and elongation protein zeta-1 (FEZ1), regulates HIV-1 trafficking...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28928208/picornaviruses-and-apoptosis-subversion-of-cell-death
#2
REVIEW
Sarah N Croft, Erin J Walker, Reena Ghildyal
Infected cells can undergo apoptosis as a protective response to viral infection, thereby limiting viral infection. As viruses require a viable cell for replication, the death of the cell limits cellular functions that are required for virus replication and propagation. Picornaviruses are single-stranded RNA viruses that modify the host cell apoptotic response, probably in order to promote viral replication, largely as a function of the viral proteases 2A, 3C, and 3CD. These proteases are essential for viral polyprotein processing and also cleave cellular proteins...
September 19, 2017: MBio
https://www.readbyqxmd.com/read/28904344/perturbed-cholesterol-and-vesicular-trafficking-associated-with-dengue-blocking-in-wolbachia-infected-aedes-aegypti-cells
#3
Vincent Geoghegan, Kirsty Stainton, Stephanie M Rainey, Thomas H Ant, Adam A Dowle, Tony Larson, Svenja Hester, Philip D Charles, Benjamin Thomas, Steven P Sinkins
Wolbachia are intracellular maternally inherited bacteria that can spread through insect populations and block virus transmission by mosquitoes, providing an important approach to dengue control. To better understand the mechanisms of virus inhibition, we here perform proteomic quantification of the effects of Wolbachia in Aedes aegypti mosquito cells and midgut. Perturbations are observed in vesicular trafficking, lipid metabolism and in the endoplasmic reticulum that could impact viral entry and replication...
September 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28902489/oral-sirna-delivery-to-treat-colorectal-liver-metastases
#4
Sung Hun Kang, Vishnu Revuri, Sang-Joon Lee, Sungpil Cho, In-Kyu Park, Kwang Jae Cho, Woo Kyun Bae, Yong-Kyu Lee
Convenient multiple dosing makes oral administration an ideal route for delivery of therapeutic siRNA. However, hostile GI environments and non-specific biological trafficking prevent from achieving appropriate bioavailability of siRNA. Here, an orally administered AuNP-siRNA-glycol chitosan-taurocholic acid nanoparticle (AR-GT NPs), was developed to selectively deliver Akt2 siRNA and treat colorectal liver metastases (CLM). AR-GT NPs are dual padlocked non-viral vectors in which the initially formed AuNP-siRNA (AR) conjugates are further encompassed by bifunctional glycol chitosan-taurocholic acid (GT) conjugates...
September 13, 2017: ACS Nano
https://www.readbyqxmd.com/read/28895884/interaction-of-recombinant-gallus-gallus-sept5-and-brain-proteins-of-h5n1-avian-influenza-virus-infected-chickens
#5
Jasmine Elanie Khairat, Vinod Balasubramaniam, Iekhsan Othman, Abdul Rahman Omar, Sharifah Syed Hassan
Septin forms a conserved family of cytoskeletal guanosine triphosphate (GTP) binding proteins that have diverse roles in protein scaffolding, vesicle trafficking, and cytokinesis. The involvement of septins in infectious viral disease pathogenesis has been demonstrated by the upregulation of SEPT5 protein and its mRNA in brain tissues of H5N1-infected chickens, thus, providing evidence for the potential importance of this protein in the pathogenesis of neurovirulence caused by the avian influenza virus. In this study, cloning, expression, and purification of Gallus gallus SEPT5 protein was performed in Escherichia coli...
September 12, 2017: Proteomes
https://www.readbyqxmd.com/read/28881492/a-novel-elane-mutation-associated-with-inflammatory-arthritis-defective-netosis-and-recurrent-parvoviral-infection
#6
Uma Thanarajasingam, Mark A Jensen, Jessica M Dorschner, Theresa Wampler Muskardin, Yogita Ghodke-Puranik, Monica Purmalek, Elias Eliopoulos, Maria I Zervou, George N Goulielmos, Matthew Howard, Mariana J Kaplan, Timothy B Niewold
OBJECTIVE: We describe a 38-year-old woman presenting with a history of inflammatory arthritis, rash and daily fevers. She was noted to have chronic parvoviral infection with persistently detectable viral titers and a novel mutation in the ELANE gene. ELANE encodes neutrophil elastase, a neutrophil serine protease with important antimicrobial effects and is found as part of neutrophil extracellular trap (NET) complexes. Pathogenic ELANE mutations have been described in forms of hereditary neutropenia...
September 7, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28874719/a-mutation-in-the-melon-vacuolar-protein-sorting-41prevents-systemic-infection-of-cucumber-mosaic-virus
#7
Ana Giner, Laura Pascual, Michael Bourgeois, Gabor Gyetvai, Pablo Rios, Belén Picó, Christelle Troadec, Abdel Bendahmane, Jordi Garcia-Mas, Ana Montserrat Martín-Hernández
In the melon exotic accession PI 161375, the gene cmv1, confers recessive resistance to Cucumber mosaic virus (CMV) strains of subgroup II. cmv1 prevents the systemic infection by restricting the virus to the bundle sheath cells and impeding viral loading to the phloem. Here we report the fine mapping and cloning of cmv1. Screening of an F2 population reduced the cmv1 region to a 132 Kb interval that includes a Vacuolar Protein Sorting 41 gene. CmVPS41 is conserved among plants, animals and yeast and is required for post-Golgi vesicle trafficking towards the vacuole...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28868514/cd161-expression-on-mucosa-associated-invariant-t-cells-is-reduced-in-hiv-infected-subjects-undergoing-antiretroviral-therapy-who-do-not-recover-cd4-t-cells
#8
Michael L Freeman, Stephen R Morris, Michael M Lederman
BACKGROUND: Mucosa-associated invariant T (MAIT) cells are a recently identified class of innate-like T cells that are involved in the mucosal immune response. MAIT cells are characterized by expression of TCR Vα7.2 and CD161. In HIV infection, there is a profound early loss of MAIT cells from the circulation that never fully recovers, even after prolonged viral control with antiretroviral therapy (ART). METHODS: We analyzed PBMCs from fresh whole blood from HIV-negative or ART-treated HIV-positive donors with full (Immune Success) or impaired (Immune Failure) CD4(+) T- cell recovery by flow cytometry for T-cell markers, TCR Vα7...
2017: Pathogens & Immunity
https://www.readbyqxmd.com/read/28867552/connexin-43-mediated-astroglial-metabolic-networks-contribute-to-the-regulation-of-the-sleep-wake-cycle
#9
Jerome Clasadonte, Eliana Scemes, Zhongya Wang, Detlev Boison, Philip G Haydon
Astrocytes produce and supply metabolic substrates to neurons through gap junction-mediated astroglial networks. However, the role of astroglial metabolic networks in behavior is unclear. Here, we demonstrate that perturbation of astroglial networks impairs the sleep-wake cycle. Using a conditional Cre-Lox system in mice, we show that knockout of the gap junction subunit connexin 43 in astrocytes throughout the brain causes excessive sleepiness and fragmented wakefulness during the nocturnal active phase. This astrocyte-specific genetic manipulation silenced the wake-promoting orexin neurons located in the lateral hypothalamic area (LHA) by impairing glucose and lactate trafficking through astrocytic networks...
September 13, 2017: Neuron
https://www.readbyqxmd.com/read/28865990/ecm-turnover-stimulated-gene-delivery-through-collagen-mimetic-peptide-plasmid-integration-in-collagen
#10
Morgan A Urello, Kristi L Kiick, Millicent O Sullivan
Gene therapies have great potential in regenerative medicine; however, clinical translation has been inhibited by low stability and limited transfection efficiencies. Herein, we incorporate collagen-mimetic peptide (CMP)-linked polyplexes in collagen scaffolds to increase DNA stability by up to 400% and enable tailorable in vivo transgene expression at 100-fold higher levels and 10-fold longer time periods. These improvements were directly linked to a sustained interaction between collagen and polyplexes that persisted during cellular remodeling, polyplex uptake, and intracellular trafficking...
September 1, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28842633/expression-and-role-of-vla-1-in-resident-memory-cd8-t-cell-responses-to-respiratory-mucosal-viral-vectored-immunization-against-tuberculosis
#11
Siamak Haddadi, Niroshan Thanthrige-Don, Sam Afkhami, Amandeep Khera, Mangalakumari Jeyanathan, Zhou Xing
Lung resident memory T cells (TRM) characterized by selective expression of mucosal integrins VLA-1 (α1β1) and CD103 (αEβ7) are generated following primary respiratory viral infections. Despite recent progress, the generation of lung TRM and the role of mucosal integrins following viral vector respiratory mucosal immunization still remains poorly understood. Here by using a replication-defective viral vector tuberculosis vaccine, we show that lung Ag-specific CD8 T cells express both VLA-1 and CD103 following respiratory mucosal immunization...
August 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28835499/nipah-and-hendra-virus-nucleoproteins-inhibit-nuclear-accumulation-of-stat1-and-stat2-by-interfering-with-their-complex-formation
#12
Akihiro Sugai, Hiroki Sato, Ikuyo Takayama, Misako Yoneda, Chieko Kai
Henipaviruses, such as Nipah (NiV) and Hendra (HeV) viruses, are highly pathogenic zoonotic agents within the Paramyxoviridae family. The phosphoprotein (P) gene products of the paramyxoviruses have been well characterized in their interferon (IFN) antagonist activity and their contribution to viral pathogenicity. In this study, we demonstrated that the nucleoprotein (N) of henipaviruses also prevents the host IFN signaling pathway. Reporter assays demonstrated that NiV and HeV N proteins (NiV-N and HeV-N, respectively) suppressed both type-I and type-II IFN responses dose-dependently, and the inhibitory effect was mediated by their core-domains...
August 23, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28835496/expression-and-subcellular-localization-of-the-kshv-k15p-protein-during-latency-and-lytic-reactivation-in-primary-effusion-lymphoma-cells
#13
Caitlin G Smith, Himanshu Kharkwal, Duncan W Wilson
The K15P membrane protein of Kaposi's sarcoma-associated herpesvirus (KSHV) interacts with multiple cellular signaling pathways, and is thought to play key roles in KSHV-associated endothelial cell angiogenesis, regulation of B-cell receptor (BCR) signaling and the survival, activation and proliferation of BCR-negative primary effusion lymphoma (PEL) cells. Although full-length K15P is ∼45kDa in size, numerous lower molecular weight forms of the protein exist as a result of differential splicing and poorly characterized post-translational processing...
August 23, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28822762/rab11a-is-required-for-porcine-reproductive-and-respiratory-syndrome-virus-induced-autophagy-to-promote-viral-replication
#14
Kai Wang, Shuaifeng Li, Tesfaye Worku, Xingjie Hao, Liaohan Yang, Shujun Zhang
Porcine reproductive and respiratory syndrome virus (PRRSV) is the leading virus known to cause massive economic loss in pig industry worldwide. In our previous study, transcriptional profiling of PRRSV-infected lung tissue of Tongcheng and Landrane pigs, which have highly pathogenic PRRSV (HP-PRRSV) susceptibility differences, showed differential expression of Rab11a. The small GTPase Rab11a regulates intracellular membrane trafficking events involved in autophagy. However, the involvement of the convergence of endosomal Rab11a and autophagy pathways during PRRSV infection is still unclear...
October 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28815417/cellular-interactome-analysis-of-vaccinia-virus-k7-protein-identifies-three-transport-machineries-as-binding-partners-for-k7
#15
Ye Li, Youyang Ke, Leiliang Zhang
Identification of viral-host interacting proteins will contribute to understanding of how poxvirus exploits the host cellular machinery. The vaccinia virus gene K7R encodes a conserved protein K7 in most orthopoxviruses. To gain insight into the biology of K7, we investigated the cellular interactome of K7 by GST pulldown coupled with mass spectrometry. The top categories of identified proteins contained components of trafficking machineries. We selected key components of three transport machineries including coatomer, retromer, and CHEVI to further confirm their binding abilities to K7...
August 16, 2017: Virus Genes
https://www.readbyqxmd.com/read/28783704/constitutive-resistance-to-viral-infection-in-human-cd141-dendritic-cells
#16
Aymeric Silvin, Chun I Yu, Xavier Lahaye, Francesco Imperatore, Jean-Baptiste Brault, Sylvain Cardinaud, Christian Becker, Wing-Hong Kwan, Cécile Conrad, Mathieu Maurin, Christel Goudot, Santy Marques-Ladeira, Yuanyuan Wang, Virginia Pascual, Esperanza Anguiano, Randy A Albrecht, Matteo Iannacone, Adolfo García-Sastre, Bruno Goud, Marc Dalod, Arnaud Moris, Miriam Merad, A Karolina Palucka, Nicolas Manel
Dendritic cells (DCs) are critical for the launching of protective T cell immunity in response to viral infection. Viruses can directly infect DCs, thereby compromising their viability and suppressing their ability to activate immune responses. How DC function is maintained in light of this paradox is not understood. By analyzing the susceptibility of primary human DC subsets to viral infections, we report that CD141(+) DCs have an innate resistance to infection by a broad range of enveloped viruses, including HIV and influenza virus...
July 7, 2017: Science Immunology
https://www.readbyqxmd.com/read/28783139/antipsychotic-induced-hdac2-transcription-via-nf-%C3%AE%C2%BAb-leads-to-synaptic-and-cognitive-side-effects
#17
Daisuke Ibi, Mario de la Fuente Revenga, Nebojsa Kezunovic, Carolina Muguruza, Justin M Saunders, Supriya A Gaitonde, José L Moreno, Maryum K Ijaz, Vishaka Santosh, Alexey Kozlenkov, Terrell Holloway, Jeremy Seto, Aintzane García-Bea, Mitsumasa Kurita, Grace E Mosley, Yan Jiang, Daniel J Christoffel, Luis F Callado, Scott J Russo, Stella Dracheva, Juan F López-Giménez, Yongchao Ge, Carlos R Escalante, J Javier Meana, Schahram Akbarian, George W Huntley, Javier González-Maeso
Antipsychotic drugs remain the standard for schizophrenia treatment. Despite their effectiveness in treating hallucinations and delusions, prolonged exposure to antipsychotic medications leads to cognitive deficits in both schizophrenia patients and animal models. The molecular mechanisms underlying these negative effects on cognition remain to be elucidated. Here we demonstrate that chronic antipsychotic drug exposure increases nuclear translocation of NF-κB in both mouse and human frontal cortex, a trafficking event triggered via 5-HT2A-receptor-dependent downregulation of the NF-κB repressor IκBα...
September 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28759649/the-tetraspanin-cd9-facilitates-mers-coronavirus-entry-by-scaffolding-host-cell-receptors-and-proteases
#18
James T Earnest, Michael P Hantak, Kun Li, Paul B McCray, Stanley Perlman, Tom Gallagher
Infection by enveloped coronaviruses (CoVs) initiates with viral spike (S) proteins binding to cellular receptors, and is followed by proteolytic cleavage of receptor-bound S proteins, which prompts S protein-mediated virus-cell membrane fusion. Infection therefore requires close proximity of receptors and proteases. We considered whether tetraspanins, scaffolding proteins known to facilitate CoV infections, hold receptors and proteases together on cell membranes. Using knockout cell lines, we found that the tetraspanin CD9, but not the tetraspanin CD81, formed cell-surface complexes of dipeptidyl peptidase 4 (DPP4), the MERS-CoV receptor, and the type II transmembrane serine protease (TTSP) member TMPRSS2, a CoV-activating protease...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28747507/roles-of-cellular-nsf-protein-in-entry-and-nuclear-egress-of-budded-virions-of-autographa-californica-multiple-nucleopolyhedrovirus
#19
Ya Guo, Qi Yue, Jinli Gao, Zhe Wang, Yun-Ru Chen, Gary W Blissard, Tong-Xian Liu, Zhaofei Li
In eukaryotic cells, the soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein receptor (SNARE) proteins comprise the minimal machinery that triggers fusion of transport vesicles with their target membranes. Comparative studies revealed that genes encoding the components of the SNARE system are highly conserved in yeast, insect, and human genomes. Upon infection of insect cells by the virus AcMNPV, the transcript levels of most SNARE genes were initially up-regulated. We found that overexpression of dominant-negative (DN) forms of NSF or knock-down of the expression of NSF, the key regulator of the SNARE system, significantly affected the infectious AcMNPV production...
July 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28724767/integrity-of-the-linker-of-nucleoskeleton-and-cytoskeleton-is-required-for-efficient-herpesvirus-nuclear-egress
#20
Barbara G Klupp, Teresa Hellberg, Harald Granzow, Kati Franzke, Beatriz Dominguez Gonzalez, Rose Goodchild, Thomas C Mettenleiter
Herpesvirus capsids assemble in the nucleus while final virion maturation proceeds in the cytoplasm. This requires that newly formed nucleocapsids cross the nuclear envelope (NE), which occurs by budding at the inner nuclear membrane (INM), release of the primary enveloped virion into the perinuclear space (PNS), and subsequent rapid fusion with the outer nuclear membrane (ONM). During this process the NE remains intact, even at late stages of infection. In addition, the spacing between the INM and ONM is maintained, as is that between the primary virion envelope and nuclear membranes...
July 19, 2017: Journal of Virology
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