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Viral trafficking

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https://www.readbyqxmd.com/read/29346349/early-treatment-of-siv-macaques-with-an-%C3%AE-4%C3%AE-7-mab-alters-virus-distribution-and-preserves-cd4-t-cells-in-later-stages-of-infection
#1
P J Santangelo, C Cicala, S N Byrareddy, K T Ortiz, D Little, K E Lindsay, S Gumber, J J Hong, K Jelicic, K A Rogers, C Zurla, F Villinger, A A Ansari, A S Fauci, J Arthos
Integrin α4β7 mediates the trafficking of leukocytes, including CD4+ T cells, to lymphoid tissues in the gut. Virus mediated damage to the gut is implicated in HIV and SIV mediated chronic immune activation and leads to irreversible damage to the immune system. We employed an immuno-PET/CT imaging technique to evaluate the impact of an anti-integrin α4β7 mAb alone or in combination with ART, on the distribution of both SIV infected cells and CD4+ cells in rhesus macaques infected with SIV. We determined that α4β7 mAb reduced viral antigen in an array of tissues of the lung, spleen, axillary, and inguinal lymph nodes...
December 20, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29342872/human-cytomegalovirus-nuclear-capsids-associate-with-the-core-nuclear-egress-complex-and-the-viral-protein-kinase-pul97
#2
Jens Milbradt, Eric Sonntag, Sabrina Wagner, Hanife Strojan, Christina Wangen, Tihana Lenac Rovis, Berislav Lisnic, Stipan Jonjic, Heinrich Sticht, William J Britt, Ursula Schlötzer-Schrehardt, Manfred Marschall
The nuclear phase of herpesvirus replication is regulated through the formation of regulatory multi-component protein complexes. Viral genomic replication is followed by nuclear capsid assembly, DNA encapsidation and nuclear egress. The latter has been studied intensely pointing to the formation of a viral core nuclear egress complex (NEC) that recruits a multimeric assembly of viral and cellular factors for the reorganization of the nuclear envelope. To date, the mechanism of the association of human cytomegalovirus (HCMV) capsids with the NEC, which in turn initiates the specific steps of nuclear capsid budding, remains undefined...
January 13, 2018: Viruses
https://www.readbyqxmd.com/read/29338048/ebola-virus-requires-a-host-scramblase-for-externalization-of-phosphatidylserine-on-the-surface-of-viral-particles
#3
Asuka Nanbo, Junki Maruyama, Masaki Imai, Michiko Ujie, Yoichiro Fujioka, Shinya Nishide, Ayato Takada, Yusuke Ohba, Yoshihiro Kawaoka
Cell surface receptors for phosphatidylserine contribute to the entry of Ebola virus (EBOV) particles, indicating that the presence of phosphatidylserine in the envelope of EBOV is important for the internalization of EBOV particles. Phosphatidylserine is typically distributed in the inner layer of the plasma membrane in normal cells. Progeny virions bud from the plasma membrane of infected cells, suggesting that phosphatidylserine is likely flipped to the outer leaflet of the plasma membrane in infected cells for EBOV virions to acquire it...
January 16, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29337164/identification-of-novel-antivirals-inhibiting-recognition-of-venezuelan-equine-encephalitis-virus-capsid-protein-by-the-importin-%C3%AE-%C3%AE-1-heterodimer-through-high-throughput-screening
#4
David R Thomas, Lindsay Lundberg, Chelsea Pinkham, Sharon Shechter, Aaron Debono, Jonathan Baell, Kylie M Wagstaff, Caroline A Hick, Kylene Kehn-Hall, David A Jans
Although the alphavirus Venezuelan equine encephalitis virus (VEEV) has been the cause of multiple outbreaks resulting in extensive human and equine mortality and morbidity, there are currently no anti-VEEV therapeutics available. VEEV pathogenicity is largely dependent on targeting of the viral capsid protein (CP) to the host cell nucleus through the nuclear transporting importin (Imp) α/β1 heterodimer. Here we perform a high-throughput screen, combined with nested counterscreens to identify small molecules able to inhibit the Impα/β1:CP interaction for the first time...
January 11, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29331069/cellular-membrane-trafficking-machineries-utilized-by-the-hepatitis-viruses
#5
REVIEW
Jun Inoue, Masashi Ninomiya, Tooru Shimosegawa, Mark A McNiven
While the life cycles of hepatitis viruses (hepatitis A, B, C, D, and E viruses) have been modestly characterized, recent intensive studies have provided new insights. Because these viruses 'hijack' the membrane trafficking of the host cell machinery during replicative propagation, it is essential to determine and understand these specific cellular pathways. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are well known as a leading cause of liver cirrhosis and hepatocellular carcinoma. While substantial inroads toward treating HCV patients have recently been made, patients with HBV continue to require life-long treatment, which makes a thorough understanding of the HBV life cycle essential...
January 13, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29327203/loss-of-cx43-mediated-functional-gap-junction-communication-in-meningeal-fibroblasts-following-mouse-hepatitis-virus-infection
#6
Abhishek Bose, Rahul Basu, Mahua Maulik, Jayasri Das Sarma
Mouse hepatitis virus (MHV) infection causes meningoencephalitis by disrupting the neuro-glial and glial-pial homeostasis. Recent studies suggest that MHV infection alters gap junction protein connexin 43 (Cx43)-mediated intercellular communication in brain and primary cultured astrocytes. In addition to astrocytes, meningeal fibroblasts also express high levels of Cx43. Fibroblasts in the meninges together with the basal lamina and the astrocyte endfeet forms the glial limitans superficialis as part of the blood-brain barrier (BBB)...
January 11, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29321327/human-papillomavirus-16-infection-induces-vap-dependent-endosomal-tubulation
#7
Abida Siddiqa, Paola Massimi, David Pim, Justyna Broniarczyk, Lawrence Banks
Human Papillomavirus (HPV) infection involves complex interactions with the endocytic transport machinery, which ultimately facilitates the entry of the incoming viral genomes into the trans-Golgi network and their subsequent nuclear entry during mitosis. The endosomal pathway is a highly dynamic intracellular transport system, which consists of vesicular compartments and tubular extensions, although it is currently unclear whether incoming viruses specifically alter the endocytic machinery. In this study, using MICAL-L1 as a marker for tubulating endosomes, we show that incoming HPV-16 virions induce a profound alteration in global levels of endocytic tubulation...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29321239/comparative-genomic-analysis-of-the-pseudofungus-hyphochytrium-catenoides
#8
Guy Leonard, Aurélie Labarre, David S Milner, Adam Monier, Darren Soanes, Jeremy G Wideman, Finlay Maguire, Sam Stevens, Divya Sain, Xavier Grau-Bové, Arnau Sebé-Pedrós, Jason E Stajich, Konrad Paszkiewicz, Matthew W Brown, Neil Hall, Bill Wickstead, Thomas A Richards
Eukaryotic microbes have three primary mechanisms for obtaining nutrients and energy: phagotrophy, photosynthesis and osmotrophy. Traits associated with the latter two functions arose independently multiple times in the eukaryotes. The Fungi successfully coupled osmotrophy with filamentous growth, and similar traits are also manifested in the Pseudofungi (oomycetes and hyphochytriomycetes). Both the Fungi and the Pseudofungi encompass a diversity of plant and animal parasites. Genome-sequencing efforts have focused on host-associated microbes (mutualistic symbionts or parasites), providing limited comparisons with free-living relatives...
January 2018: Open Biology
https://www.readbyqxmd.com/read/29288344/fdc-tfh-interactions-within-cervical-lymph-nodes-of-siv-infected-rhesus-macaques
#9
Rajnish S Dave, Ravi K Sharma, Roshell R Muir, Elias Haddad, Sanjeev Gumber, Francois Villinger, Artinder P Nehra, Zafar K Khan, Brian Wigdahl, Aftab A Ansari, Siddappa N Byrareddy, Pooja Jain
Cerebrospinal fluid (CSF) drains via the lymphatic drainage pathway. This lymphatic pathway connects the central nervous system (CNS) to the cervical lymph node (CLN). As the CSF drains to CLN via the dural and nasal lymphatics, T cells and antigen presenting cells pass along the channels from the subarachnoid space through the cribriform plate. Human immunodeficiency virus (HIV) may also egress from the CNS along this pathway. As a result, HIV egressing from the CNS may accumulate within the CLN. Towards this objective, we analyzed CLNs isolated from rhesus macaques that were chronically-infected with simian immunodeficiency virus (SIV)...
December 29, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/29274410/cd151-a-novel-host-factor-of-nuclear-export-signaling-in-influenza-virus-infection
#10
Yongkang Qiao, Yan Yan, Kai Sen Tan, Sheryl Sl Tan, Ju Ee Seet, Thiruma Valavan Arumugam, Vincent Tk Chow, De Yun Wang, Thai Tran
BACKGROUND: Despite advances in our understanding of the mechanisms of influenza A virus (IAV) infection, the crucial virus-host interactions during the viral replication cycle still remain incomplete. Tetraspanin CD151 is highly expressed in the human respiratory tract, but its pathological role in IAV infection is unknown. OBJECTIVES: To characterize the functional role and mechanisms of action of CD151 in IAV infection of the upper and lower respiratory tracts with H1N1 and H3N2 strains...
December 20, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29259099/il-2r%C3%AE-abundance-differentially-tunes-il-2-signaling-dynamics-in-cd4-and-cd8-t-cells
#11
Geoffrey A Smith, Jack Taunton, Arthur Weiss
Interleukin-2 (IL-2) stimulates both activated CD4+ and CD8+ T cells to proliferate. IL-2 signals through an identical receptor complex and promotes the same dose-dependent phosphorylation of the canonical transcription factor STAT5 in both cell types. Despite this, CD8+ T cells enter the S phase earlier and proliferate to a greater extent than do CD4+ T cells in response to IL-2. We identified distinct IL-2 signaling dynamics in CD4+ and CD8+ T cells. In IL-2-stimulated CD8+ T cells, STAT5 phosphorylation increased rapidly and was sustained for 6 hours...
December 19, 2017: Science Signaling
https://www.readbyqxmd.com/read/29237840/human-cytomegalovirus-ul111a-and-us27-gene-products-enhance-the-cxcl12-cxcr4-signaling-axis-via-distinct-mechanisms
#12
Carolyn C Tu, Kathleen L Arnolds, Christine M O'Connor, Juliet V Spencer
Human cytomegalovirus (HCMV) is a prevalent pathogen that establishes lifelong infection in the host. Virus persistence is aided by extensive manipulation of the host immune system, particularly cytokine and chemokine signaling pathways. The HCMV UL111A gene encodes cmvIL-10, an ortholog of human interleukin-10 that has many immunomodulatory effects. We found that cmvIL-10 increased signaling outcomes from human CXCR4, a chemokine receptor with essential roles in hematopoiesis and immune cell trafficking, in response to its natural ligand CXCL12...
December 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29237720/beyond-self-eating-the-control-of-nonautophagic-functions-and-signaling-pathways-by-autophagy-related-proteins
#13
REVIEW
Ken Cadwell, Jayanta Debnath
The identification of conserved autophagy-related proteins (ATGs) that mediate bulk degradation of cytosolic material laid the foundation for breakthroughs linking autophagy to a litany of physiological processes and disease conditions. Recent discoveries are revealing that these same ATGs orchestrate processes that are related to, and yet clearly distinct from, classic autophagy. Autophagy-related functions include secretion, trafficking of phagocytosed material, replication and egress of viral particles, and regulation of inflammatory and immune signaling cascades...
December 13, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29226179/virus-binding-and-internalization-assay-for-adeno-associated-virus
#14
Garrett E Berry, Longping V Tse
The binding and internalization of adeno-associated virus (AAV) is an important determinant of viral infectivity and tropism. The ability to dissect these two tightly connected cellular processes would allow better understanding and provide insight on virus entry and trafficking. In the following protocol, we describe a quantitative PCR (qPCR) based method to determine the amount of vector bound to the cell surface and the amount of subsequent virus internalization based on viral genome quantification. This protocol is optimized for studying AAV...
January 20, 2017: Bio-protocol
https://www.readbyqxmd.com/read/29215797/rubicon-lc3-associated-phagocytosis-and-beyond
#15
REVIEW
Sing-Wai Wong, Payel Sil, Jennifer Martinez
Rubicon (Rubcn) was initially identified as a component of the Class III PI3K complex and a negative regulator of canonical autophagy and endosomal trafficking. However, Rubicon has attracted the most notoriety because of its critical role in LC3-associated phagocytosis (LAP), a form of non-canonical autophagy that utilizes some components of the autophagy machinery to process extracellular cargo. Additionally, Rubicon has been identified as a key modulator of the inflammatory response and viral replication...
December 7, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29215074/structural-analysis-of-the-complex-between-influenza-b-nucleoprotein-and-human-importin-%C3%AE
#16
Alice Labaronne, Sigrid Milles, Amélie Donchet, Malene Ringkjøbing Jensen, Martin Blackledge, Jean-Marie Bourhis, Rob W H Ruigrok, Thibaut Crépin
Influenza viruses are negative strand RNA viruses that replicate in the nucleus of the cell. The viral nucleoprotein (NP) is the major component of the viral ribonucleoprotein. In this paper we show that the NP of influenza B has a long N-terminal tail of 70 residues with intrinsic flexibility. This tail contains the Nuclear Location Signal (NLS). The nuclear trafficking of the viral components mobilizes cellular import factors at different stages, making these host-pathogen interactions promising targets for new therapeutics...
December 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29212940/hiv-1-envelope-glycoprotein-trafficking-through-the-endosomal-recycling-compartment-is-required-for-particle-incorporation
#17
Junghwa Kirschman, Mingli Qi, Lingmei Ding, Jason Hammonds, Krista Dienger-Stambaugh, Jaang-Jiun Wang, Lynne A Lapierre, James R Goldenring, Paul Spearman
The HIV-1 envelope glycoprotein (Env) encodes specific trafficking signals within its long cytoplasmic tail (CT) that regulate incorporation into HIV-1 particles. Rab11-Family Interacting Protein 1C (FIP1C) and Rab14 are host trafficking factors required for Env particle incorporation, suggesting that Env undergoes sorting from the endosomal recycling compartment (ERC) to the site of particle assembly on the plasma membrane. We disrupted outward sorting from the ERC by expressing a C-terminal fragment of FIP1C (FIP1C560-649) and examined the consequences on Env trafficking and incorporation into particles...
December 6, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29207600/host-cell-transcriptome-modification-upon-exogenous-hpv16-l2-protein-expression
#18
Xinwei An, Yuhan Hao, Patricio I Meneses
Human papillomavirus type 16 minor capsid protein L2 has been shown to assist in the initial entry and intracellular trafficking events leading to nuclear translocation of the viral genome. During our investigations of L2 function, we observed that expression of L2 in a keratinocyte cell line (HaCaT) resulted in phenotypic changes. In this manuscript, we present data that expression of the L2 protein in this cellular model system HaCaTs resulted in a shift from G0/G1 phase to mitotic S phase, as well as a reduced amount of retinoblastoma protein (Rb) and an increase in Cdc2 phosphorylation...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29207511/subcellular-trafficking-of-the-papillomavirus-genome-during-initial-infection-the-remarkable-abilities-of-minor-capsid-protein-l2
#19
REVIEW
Samuel K Campos
Since 2012, our understanding of human papillomavirus (HPV) subcellular trafficking has undergone a drastic paradigm shift. Work from multiple laboratories has revealed that HPV has evolved a unique means to deliver its viral genome (vDNA) to the cell nucleus, relying on myriad host cell proteins and processes. The major breakthrough finding from these recent endeavors has been the realization of L2-dependent utilization of cellular sorting factors for the retrograde transport of vDNA away from degradative endo/lysosomal compartments to the Golgi, prior to mitosis-dependent nuclear accumulation of L2/vDNA...
December 3, 2017: Viruses
https://www.readbyqxmd.com/read/29204145/molecular-signatures-of-immunity-and-immunogenicity-in-infection-and-vaccination
#20
REVIEW
Mariëlle C Haks, Barbara Bottazzi, Valentina Cecchinato, Corinne De Gregorio, Giuseppe Del Giudice, Stefan H E Kaufmann, Antonio Lanzavecchia, David J M Lewis, Jeroen Maertzdorf, Alberto Mantovani, Federica Sallusto, Marina Sironi, Mariagrazia Uguccioni, Tom H M Ottenhoff
Vaccinology aims to understand what factors drive vaccine-induced immunity and protection. For many vaccines, however, the mechanisms underlying immunity and protection remain incompletely characterized at best, and except for neutralizing antibodies induced by viral vaccines, few correlates of protection exist. Recent omics and systems biology big data platforms have yielded valuable insights in these areas, particularly for viral vaccines, but in the case of more complex vaccines against bacterial infectious diseases, understanding is fragmented and limited...
2017: Frontiers in Immunology
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