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https://www.readbyqxmd.com/read/29142129/entry-of-human-coronavirus-nl63-to-the-cell
#1
Aleksandra Milewska, Paulina Nowak, Katarzyna Owczarek, Artur Szczepanski, Miroslaw Zarebski, Agnieszka Hoang-Bujnowicz, Krzysztof Berniak, Jacek Wojarski, Slawomir Zeglen, Zbigniew Baster, Zenon Rajfur, Krzysztof Pyrc
First steps of human coronavirus NL63 (HCoV-NL63) infection were previously described. The virus binds to target cells by heparan sulfate proteoglycans, and interacts with the ACE2 protein. Subsequent events, including virus internalization and trafficking, remain to be elucidated. In this study, we mapped the process of HCoV-NL63 entry into LLC-Mk2 cell line and ex vivo 3D tracheobronchial tissue.Using a variety of techniques we have shown that HCoV-NL63 virions require endocytosis for successful entry to the LLC-MK2 cells, and interaction between the virus and the ACE2 molecule triggers recruitment of clathrin...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29132390/a-transwell-assay-that-excludes-exosomes-for-assessment-of-tunneling-nanotube-mediated-intercellular-communication
#2
Venugopal Thayanithy, Patrick O'Hare, Phillip Wong, Xianda Zhao, Clifford J Steer, Subbaya Subramanian, Emil Lou
BACKGROUND: Tunneling nanotubes (TNTs) are naturally-occurring filamentous actin-based membranous extensions that form across a wide spectrum of mammalian cell types to facilitate long-range intercellular communication. Valid assays are needed to accurately assess the downstream effects of TNT-mediated transfer of cellular signals in vitro. We recently reported a modified transwell assay system designed to test the effects of intercellular transfer of a therapeutic oncolytic virus, and viral-activated drugs, between cells via TNTs...
November 13, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29128397/identification-and-characterization-of-molluscan-caveolin-1-ortholog-from-haliotis-discus-discus-possible-involvement-in-embryogenesis-and-host-defense-mechanism-against-pathogenic-stress
#3
H M V Udayantha, S D N K Bathige, Thanthrige Thiunuwan Priyathilaka, Sukkyoung Lee, Myoung-Jin Kim, Jehee Lee
Caveolins are principal membrane proteins of caveolae that play a central role in signal transduction, substrate transport, and membrane trafficking in various cell types. Numerous studies have reported the crucial role of caveolin-1 (CAV1) in response to invading microbes; yet, very little is known about molluscan CAV1. In this study, we identified and characterized CAV1 ortholog from the disk abalone, Haliotis discus discus (HdCAV1). The cDNA sequence of HdCAV1 is 826 bp long and encodes a 127-amino acid polypeptide...
November 8, 2017: Gene Expression Patterns: GEP
https://www.readbyqxmd.com/read/29116194/site-specific-modification-of-adeno-associated-virus-enables-both-fluorescent-imaging-of-viral-particles-and-characterization-of-the-capsid-interactome
#4
Jayanth S Chandran, Paul S Sharp, Evangelia Karyka, João Miguel da Conceição Aves-Cruzeiro, Ian Coldicott, Lydia Castelli, Guillaume Hautbergue, Mark O Collins, Mimoun Azzouz
Adeno-associated viruses (AAVs) are attractive gene therapy vectors due to their low toxicity, high stability, and rare integration into the host genome. Expressing ligands on the viral capsid can re-target AAVs to new cell types, but limited sites have been identified on the capsid that tolerate a peptide insertion. Here, we incorporated a site-specific tetracysteine sequence into the AAV serotype 9 (AAV9) capsid, to permit labelling of viral particles with either a fluorescent dye or biotin. We demonstrate that fluorescently labelled particles are detectable in vitro, and explore the utility of the method in vivo in mice with time-lapse imaging...
November 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29113920/intracellular-trafficking-of-a-dynein-based-nanoparticle-designed-for-gene-delivery
#5
Marianna Teixeira de Pinho Favaro, Ugutz Unzueta, Martí de Cabo, Antonio Villaverde, Neus Ferrer-Miralles, Adriano Rodrigues Azzoni
The success of viruses in the delivery of the viral genome to target cells relies on the evolutionary selection of protein-based domains able to hijack the intermolecular interactions through which cells respond to intra- and extracellular stimuli. In an effort to mimic viral infection capabilities during non-viral gene delivery, a modular recombinant protein named T-Rp3 was recently developed, containing a DNA binding domain, a dynein molecular motor interacting domain, and a TAT-derived transduction domain...
November 4, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29097707/gp73-regulates-hepatic-steatosis-by-enhancing-scap-srebps-interaction
#6
Xiaoli Yang, Feixiang Wu, Jiankang Chen, Cui Wang, Yongjie Zhu, Feng Li, Qinfang Hao, Cuijuan Duan, Li Wang, Xueping Ma, Deyong Zou, Li Luo, Yiwen Zhao, Kai Guan, Yuan Cao, Pingping Zhang, Pengyu Zhou, Shengli Ma, Zhifeng Yan, Jia Li, Yanhong Zhang, Congwen Wei, Hui Zhong
Elevated Golgi phosphoprotein 2 (GP73, also known as GOLPH2 or GOLM1) expression in serum and liver, which can be induced by viral infection and cytokine treatments, is intimately connected with liver disease, including acute hepatitis, cirrhosis and hepatocellular carcinoma (HCC). However, its pathogenic roles in hepatic diseases have never been clarified in detail. Here, we showed that the upregulated GP73 is indispensable for SREBPs activation and lipogenesis. Notably, GP73 overexpression enhanced SCAP-SREBPs binding and its Golgi trafficking even under cholesterol sufficiency...
November 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29093729/an-update-on-the-intracellular-and-intercellular-trafficking-of-carmoviruses
#7
REVIEW
José A Navarro, Vicente Pallás
Despite harboring the smallest genomes among plant RNA viruses, carmoviruses have emerged as an ideal model system for studying essential steps of the viral cycle including intracellular and intercellular trafficking. Two small movement proteins, formerly known as double gene block proteins (DGBp1 and DGBp2), have been involved in the movement throughout the plant of some members of carmovirus genera. DGBp1 RNA-binding capability was indispensable for cell-to-cell movement indicating that viral genomes must interact with DGBp1 to be transported...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29080420/activation-and-trafficking-of-cd8-t-cells-during-viral-skin-infection-immunological-lessons-learned-from-vaccinia-virus
#8
REVIEW
Samuel J Hobbs, Jossef F Osborn, Jeffrey C Nolz
Epicutaneous delivery of vaccinia virus (VacV) by scarification of the skin generates robust and durable protective immunity, which was ultimately responsible for eradicating smallpox from the human race. Therefore, infection of the skin with VacV is often used in experimental model systems to study the activation of adaptive immunity, as well as the development and functional features of immunological memory. Here, we describe recent advances using this viral infection to identify and characterize the mechanisms regulating the activation and trafficking of cytotoxic CD8(+) T cells into the inflamed skin, the migratory features of CD8(+) T cells within the skin microenvironment, and finally, their subsequent differentiation into tissue-resident memory cells...
October 24, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/29075278/hop-sti1-a-two-faced-cochaperone-involved-in-pattern-recognition-receptor-maturation-and-viral-infection
#9
Christian E Lamm, Max E Kraner, Jörg Hofmann, Frederik Börnke, Hans-Peter Mock, Uwe Sonnewald
Perception of pathogens by host pattern recognition receptors (PRRs) or R proteins is a prerequisite to promote successful immune responses. The Hsp70/Hsp90 organizing protein Hop/Sti1, a multifunctional cochaperone, has been implicated in the maturation of a receptor-like kinase (RLK) necessary for chitin sensing. However, it remains unknown whether Hop/Sti1 is generally participating in PRR genesis. Using RNA-interference (RNAi), we silenced Hop/Sti1 expression in Nicotiana tabacum to gain further insight into the role of the cochaperone in plant defense responses...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29061883/kif13a-mediates-influenza-a-virus-ribonucleoproteins-trafficking
#10
Ana Ramos-Nascimento, Bárbara Kellen, Filipe Ferreira, Marta Alenquer, Silvia Vale-Costa, Graça Raposo, Cédric Delevoye, Maria João Amorim
Influenza A is a rapid evolving virus, successful in provoking periodic epidemics and occasional pandemics in humans. Viral assembly is complex as the virus incorporates an eight-partite segmented genome of RNA (in the form of viral ribonucleoproteins, vRNPs). Genome assembly, with implications to public health, is not completely understood. It was reported that vRNPs are transported to the cell surface on Rab11 vesicles using microtubules, but no molecular motor has been assigned to the process. Here, we have identified KIF13A, a member of the kinesin-3 family, as the first molecular motor efficiently transporting vRNP-Rab11 vesicles during IAV infection...
October 23, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29056673/feline-immunodeficiency-virus-neuropathogenesis-a-model-for-hiv-induced-cns-inflammation-and-neurodegeneration
#11
REVIEW
Rick B Meeker, Lola Hudson
Feline Immunodeficiency virus (FIV), similar to its human analog human immunodeficiency virus (HIV), enters the central nervous system (CNS) soon after infection and establishes a protected viral reservoir. The ensuing inflammation and damage give rise to varying degrees of cognitive decline collectively known as HIV-associated neurocognitive disorders (HAND). Because of the similarities to HIV infection and disease, FIV has provided a useful model for both in vitro and in vivo studies of CNS infection, inflammation and pathology...
March 6, 2017: Veterinary Sciences
https://www.readbyqxmd.com/read/29053588/yeast-killer-toxin-k28-biology-and-unique-strategy-of-host-cell-intoxication-and-killing
#12
REVIEW
Björn Becker, Manfred J Schmitt
The initial discovery of killer toxin-secreting brewery strains of Saccharomyces cerevisiae (S. cerevisiae) in the mid-sixties of the last century marked the beginning of intensive research in the yeast virology field. So far, four different S. cerevisiae killer toxins (K28, K1, K2, and Klus), encoded by cytoplasmic inherited double-stranded RNA viruses (dsRNA) of the Totiviridae family, have been identified. Among these, K28 represents the unique example of a yeast viral killer toxin that enters a sensitive cell by receptor-mediated endocytosis to reach its intracellular target(s)...
October 20, 2017: Toxins
https://www.readbyqxmd.com/read/29046458/a-tyrosine-based-trafficking-motif-of-the-tegument-protein-pul71-is-crucial-for-human-cytomegalovirus-secondary-envelopment
#13
Andrea N Dietz, Clarissa Villinger, Stefan Becker, Manfred Frick, Jens von Einem
The human cytomegalovirus (HCMV) tegument protein pUL71 is required for efficient secondary envelopment and accumulates at the Golgi-derived viral assembly complex (vAC) during infection. Analysis of various C-terminally truncated pUL71 fused to eGFP identified amino acids 23-34 as important determinants for its Golgi localization. Sequence analysis and mutational verification revealed the presence of an N-terminal tyrosine-based trafficking motif (YxxΦ) in pUL71. This led us to hypothesize a requirement of the YxxΦ motif for the function of pUL71 in infection...
October 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29038250/inhibition-of-irak1-ubiquitination-determines-glucocorticoid-sensitivity-for-tlr9-induced-inflammation-in-macrophages
#14
Fansheng Kong, Zhiwei Liu, Viral G Jain, Kenjiro Shima, Takuji Suzuki, Louis J Muglia, Daniel T Starczynowski, Chandrashekhar Pasare, Sandip Bhattacharyya
Inflammatory responses are controlled by signaling mediators that are regulated by various posttranslational modifications. Recently, transcription-independent functions for glucocorticoids (GC) in restraining inflammation have emerged, but the underlying mechanisms are unknown. In this study, we report that GC receptor (GR)-mediated actions of GC acutely suppress TLR9-induced inflammation via inhibition of IL-1R-associated kinase 1 (IRAK1) ubiquitination. β-TrCP-IRAK1 interaction is required for K48-linked ubiquitination of IRAK1 at Lys(134) and subsequent membrane-to-cytoplasm trafficking of IRAK1 interacting partners TNFR-associated factor 6 and TAK1 that facilitates NF-κB and MAPK activation...
November 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29037245/reduced-antiretroviral-drug-efficacy-and-concentration-in-hiv-infected-microglia-contributes-to-viral-persistence-in-brain
#15
Eugene L Asahchop, Oussama Meziane, Manmeet K Mamik, Wing F Chan, William G Branton, Lothar Resch, M John Gill, Elie Haddad, Jean V Guimond, Mark A Wainberg, Glen B Baker, Eric A Cohen, Christopher Power
BACKGROUND: In patients with HIV/AIDS receiving antiretroviral therapy (ART), HIV-1 persistence in brain tissue is a vital and unanswered question. HIV-1 infects and replicates in resident microglia and trafficking macrophages within the brain although the impact of individual ART drugs on viral infection within these brain myeloid cells is unknown. Herein, the effects of contemporary ART drugs were investigated using in vitro and in vivo models of HIV-1 brain infection. RESULTS: The EC50 values for specific ART drugs in HIV-infected human microglia were significantly higher compared to bone marrow-derived macrophages and peripheral blood mononuclear cells...
October 16, 2017: Retrovirology
https://www.readbyqxmd.com/read/29033128/the-dna-inflammasome-in-human-myeloid-cells-is-initiated-by-a-sting-cell-death-program-upstream-of-nlrp3
#16
Moritz M Gaidt, Thomas S Ebert, Dhruv Chauhan, Katharina Ramshorn, Francesca Pinci, Sarah Zuber, Fionan O'Duill, Jonathan L Schmid-Burgk, Florian Hoss, Raymund Buhmann, Georg Wittmann, Eicke Latz, Marion Subklewe, Veit Hornung
Detection of cytosolic DNA constitutes a central event in the context of numerous infectious and sterile inflammatory conditions. Recent studies have uncovered a bipartite mode of cytosolic DNA recognition, in which the cGAS-STING axis triggers antiviral immunity, whereas AIM2 triggers inflammasome activation. Here, we show that AIM2 is dispensable for DNA-mediated inflammasome activation in human myeloid cells. Instead, detection of cytosolic DNA by the cGAS-STING axis induces a cell death program initiating potassium efflux upstream of NLRP3...
November 16, 2017: Cell
https://www.readbyqxmd.com/read/29031163/ebola-virus-requires-phosphatidylinositol-3-5-bisphosphate-production-for-efficient-viral-entry
#17
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/29028839/interaction-of-the-human-respiratory-syncytial-virus-matrix-protein-with-cellular-adaptor-protein-complex-3-plays-a-critical-role-in-trafficking
#18
Casey Ward, Maciej Maselko, Christopher Lupfer, Meagan Prescott, Manoj K Pastey
Human Respiratory Syncytial Virus (HRSV) is a leading cause of bronchopneumonia in infants and the elderly. To date, knowledge of viral and host protein interactions within HRSV is limited and are critical areas of research. Here, we show that HRSV Matrix (M) protein interacts with the cellular adaptor protein complex 3 specifically via its medium subunit (AP-3Mu3A). This novel protein-protein interaction was first detected via yeast-two hybrid screen and was further confirmed in a mammalian system by immunofluorescence colocalization and co-immunoprecipitation...
2017: PloS One
https://www.readbyqxmd.com/read/28989857/jc-polyomavirus-attachment-and-entry-potential-sites-for-pml-therapeutics
#19
Colleen L Mayberry, Christian D S Nelson, Melissa S Maginnis
PURPOSE OF REVIEW: JC polyomavirus (JCPyV) is a significant human pathogen that causes an asymptomatic infection in the kidney in the majority of the population. In immunosuppressed individuals, the virus can become reactivated and spread to the brain, causing the fatal, demyelinating disease progressive multifocal leukoencephalopathy (PML). There are currently limited treatment options for this fatal disease. Attachment to receptors and entry into host cells are the initiating events in JCPyV infection and therefore an attractive target for therapeutics to prevent or treat PML...
September 2017: Current Clinical Microbiology Reports
https://www.readbyqxmd.com/read/28978712/full-length-isoforms-of-kshv-lana-accumulate-in-the-cytoplasm-of-cells-undergoing-the-lytic-cycle-of-replication
#20
H Jacques Garrigues, Kellie Howard, Serge Barcy, Minako Ikoma, Ashlee V Moses, Gail H Deutsch, David Wu, Keiji Ueda, Timothy M Rose
The latency-associated nuclear antigen (LANA) of the Kaposi sarcoma herpesvirus (KSHV) performs a variety of functions to establish and maintain KSHV latency. During latency, LANA localizes to discrete punctate spots in the nucleus where it tethers viral episomes to cellular chromatin and interacts with nuclear components to regulate cellular and viral gene expression. Using highly sensitive tyramide signal amplification (TSA), we determined that LANA localizes to the cytoplasm in different cell types undergoing the lytic cycle of replication after de novo primary infection and after spontaneous, TPA-, or ORF50/RTA-induced activation...
October 4, 2017: Journal of Virology
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