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https://www.readbyqxmd.com/read/27909702/complement-inhibition-enables-tumor-delivery-of-lcmv-glycoprotein-pseudotyped-viruses-in-the-presence-of-antiviral-antibodies
#1
Laura Evgin, Carolina S Ilkow, Marie-Claude Bourgeois-Daigneault, Christiano Tanese de Souza, Lawton Stubbert, Michael S Huh, Victoria A Jennings, Monique Marguerie, Sergio A Acuna, Brian A Keller, Charles Lefebvre, Theresa Falls, Fabrice Le Boeuf, Rebecca A Auer, John D Lambris, J Andrea McCart, David F Stojdl, John C Bell
The systemic delivery of therapeutic viruses, such as oncolytic viruses or vaccines, is limited by the generation of neutralizing antibodies. While pseudotyping of rhabdoviruses with the lymphocytic choriomeningitis virus glycoprotein has previously allowed for multiple rounds of delivery in mice, this strategy has not translated to other animal models. For the first time, we provide experimental evidence that antibodies generated against the lymphocytic choriomeningitis virus glycoprotein mediate robust complement-dependent viral neutralization via activation of the classical pathway...
2016: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/27872905/interferon-driven-deletion-of-antiviral-b-cells-at-the-onset-of-chronic-infection
#2
Benedict Fallet, Kerstin Narr, Yusuf I Ertuna, Melissa Remy, Rami Sommerstein, Karen Cornille, Mario Kreutzfeldt, Nicolas Page, Gert Zimmer, Florian Geier, Tobias Straub, Hanspeter Pircher, Kevin Larimore, Philip D Greenberg, Doron Merkler, Daniel D Pinschewer
Inadequate antibody responses and perturbed B cell compartments represent hallmarks of persistent microbial infections, but the mechanisms whereby persisting pathogens suppress humoral immunity remain poorly defined. Using adoptive transfer experiments in the context of a chronic lymphocytic choriomeningitis virus (LCMV) infection of mice, we have documented rapid depletion of virus-specific B cells that coincided with the early type I interferon response to infection. We found that the loss of activated B cells was driven by type I interferon (IFN-I) signaling to several cell types including dendritic cells, T cells and myeloid cells...
October 21, 2016: Science Immunology
https://www.readbyqxmd.com/read/27868108/inflammatory-monocytes-hinder-antiviral-b-cell-responses
#3
Stefano Sammicheli, Mirela Kuka, Pietro Di Lucia, Nereida Jimenez de Oya, Marco De Giovanni, Jessica Fioravanti, Claudia Cristofani, Carmela G Maganuco, Benedict Fallet, Lucia Ganzer, Laura Sironi, Marta Mainetti, Renato Ostuni, Kevin Larimore, Philip D Greenberg, Juan Carlos de la Torre, Luca G Guidotti, Matteo Iannacone
Antibodies are critical for protection against viral infections. However, several viruses, such as lymphocytic choriomeningitis virus (LCMV), avoid the induction of early protective antibody responses by poorly understood mechanisms. Here we analyzed the spatiotemporal dynamics of B cell activation to show that, upon subcutaneous infection, LCMV-specific B cells readily relocate to the interfollicular and T cell areas of the draining lymph node where they extensively interact with CD11b(+)Ly6C(hi) inflammatory monocytes...
October 21, 2016: Science Immunology
https://www.readbyqxmd.com/read/27861803/%C3%AE-4-%C3%AE-1-integrin-promotes-accumulation-of-tissue-resident-memory-cd8-t-cells-in-salivary-glands
#4
Sandra Woyciechowski, Maike Hofmann, Hanspeter Pircher
The salivary glands (SGs) of virus-immune mice contain substantial numbers of tissue-resident memory CD8(+) T cells (TRM cells) that can provide immunity to local infections. Integrins regulate entry of activated T cells into non-lymphoid tissues but the molecules that mediate migration of virus-specific CD8(+) T cells to the SGs have not yet been defined. Here, we found that polyinosinic-polycytidylic acid (poly(I:C)) strongly promoted the accumulation of P14 TCR-transgenic CD8(+) TRM cells in SGs in an α4 β1 integrin-dependent manner...
November 11, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27861537/modelling-and-simulation-of-the-dynamics-of-the-antigen-specific-t-cell-response-using-variable-structure-control-theory
#5
Anet J N Anelone, Sarah K Spurgeon
Experimental and mathematical studies in immunology have revealed that the dynamics of the programmed T cell response to vigorous infection can be conveniently modelled using a sigmoidal or a discontinuous immune response function. This paper hypothesizes strong synergies between this existing work and the dynamical behaviour of engineering systems with a variable structure control (VSC) law. These findings motivate the interpretation of the immune system as a variable structure control system. It is shown that dynamical properties as well as conditions to analytically assess the transition from health to disease can be developed for the specific T cell response from the theory of variable structure control...
2016: PloS One
https://www.readbyqxmd.com/read/27855284/development-of-live-attenuated-arenavirus-vaccines-based-on-codon-deoptimization-of-the-viral-glycoprotein
#6
Benson Y H Cheng, Aitor Nogales, Juan Carlos de la Torre, Luis Martínez-Sobrido
Several arenaviruses, chiefly Lassa (LASV) in West Africa, cause hemorrhagic fever (HF) disease in humans and pose important public health problems in their endemic regions. To date, there are no FDA-approved arenavirus vaccines and current anti-arenaviral therapy is limited to the use of ribavirin that has very limited efficacy. In this work we document that a recombinant prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) with a codon deoptimized (CD) surface glycoprotein (GP), rLCMV/CD, exhibited wild type (WT)-like growth properties in cultured cells despite barely detectable GP expression levels in rLCMV/CD-infected cells...
November 14, 2016: Virology
https://www.readbyqxmd.com/read/27852793/dampened-antiviral-immunity-to-intravaginal-exposure-to-rna-viral-pathogens-allows-enhanced-viral-replication
#7
Shahzada Khan, Erik M Woodruff, Martin Trapecar, Krystal A Fontaine, Ashley Ezaki, Timothy C Borbet, Melanie Ott, Shomyseh Sanjabi
Understanding the host immune response to vaginal exposure to RNA viruses is required to combat sexual transmission of this class of pathogens. In this study, using lymphocytic choriomeningitis virus (LCMV) and Zika virus (ZIKV) in wild-type mice, we show that these viruses replicate in the vaginal mucosa with minimal induction of antiviral interferon and inflammatory response, causing dampened innate-mediated control of viral replication and a failure to mature local antigen-presenting cells (APCs). Enhancement of innate-mediated inflammation in the vaginal mucosa rescues this phenotype and completely inhibits ZIKV replication...
November 16, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27812556/type-i-interferon-suppresses-virus-specific-b-cell-responses-by-modulating-cd8-t-cell-differentiation
#8
E Ashley Moseman, Tuoqi Wu, Juan Carlos de la Torre, Pamela L Schwartzberg, Dorian B McGavern
Studies have established a role for T cells in resolving persistent viral infections, yet emerging evidence indicates that both T and B cells are required to control some viruses. During persistent infection, a marked lag or failure to generate neutralizing antibodies is commonly observed and likely contributes to an inability to control certain pathogens. Using lymphocytic choriomeningitis virus (LCMV) as a model, we have examined how a persistent viral infection can suppress neutralizing humoral immunity...
October 2016: Science Immunology
https://www.readbyqxmd.com/read/27812182/liver-monocytes-and-kupffer-cells-remain-transcriptionally-distinct-during-chronic-viral-infection
#9
Martijn D B van de Garde, Dowty Movita, Marieke van der Heide, Florence Herschke, Sandra De Jonghe, Lucio Gama, Andre Boonstra, Thomas Vanwolleghem
Due to the scarcity of immunocompetent animal models for chronic viral hepatitis, little is known about the role of the innate intrahepatic immune system during viral replication in the liver. These insights are however fundamental for the understanding of the inappropriate adaptive immune responses during the chronic phase of the infection. We apply the Lymphocytic Choriomenigitis Virus (LCMV) clone 13 mouse model to examine chronic virus-host interactions of Kupffer cells (KC) and infiltrating monocytes (IM) in an infected liver...
2016: PloS One
https://www.readbyqxmd.com/read/27809306/cd169-macrophages-regulate-pd-l1-expression-via-type-i-interferon-and-thereby-prevent-severe-immunopathology-after-lcmv-infection
#10
Namir Shaabani, Vikas Duhan, Vishal Khairnar, Asmae Gassa, Rita Ferrer-Tur, Dieter Häussinger, Mike Recher, Gennadiy Zelinskyy, Jia Liu, Ulf Dittmer, Mirko Trilling, Stefanie Scheu, Cornelia Hardt, Philipp A Lang, Nadine Honke, Karl S Lang
Upon infection with persistence-prone virus, type I interferon (IFN-I) mediates antiviral activity and also upregulates the expression of programmed death ligand 1 (PD-L1), and this upregulation can lead to CD8(+) T-cell exhaustion. How these very diverse functions are regulated remains unknown. This study, using the lymphocytic choriomeningitis virus, showed that a subset of CD169(+) macrophages in murine spleen and lymph nodes produced high amounts of IFN-I upon infection. Absence of CD169(+) macrophages led to insufficient production of IFN-I, lower antiviral activity and persistence of virus...
November 3, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27807227/heterologous-immunity-and-persistent-murine-cytomegalovirus-infection
#11
Jenny W Che, Keith A Daniels, Liisa K Selin, Raymond M Welsh
: One's history of infections can affect the immune response to unrelated pathogens and influence disease outcome through the process of heterologous immunity. This can occur after acute viral infections, such as lymphocytic choriomeningitis virus (LCMV) and vaccinia virus, where the pathogens are cleared, but it becomes a more complex issue in the context of persistent infections. In this study, murine cytomegalovirus (MCMV) was used as a persistent infection model to study heterologous immunity with LCMV...
November 2, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27799548/ptpn22-contributes-to-exhaustion-of-t-lymphocytes-during-chronic-viral-infection
#12
Christian J Maine, John R Teijaro, Kristi Marquardt, Linda A Sherman
The protein encoded by the autoimmune-associated protein tyrosine phosphatase nonreceptor type 22 gene, PTPN22, has wide-ranging effects in immune cells including suppression of T-cell receptor signaling and promoting efficient production of type I interferons (IFN-I) by myeloid cells. Here we show that mice deficient in PTPN22 resist chronic viral infection with lymphocytic choriomeningitis virus clone 13 (LCMV cl13). The numbers and function of viral-specific CD4 T lymphocytes is greatly enhanced, whereas expression of the IFNβ-induced IL-2 repressor, cAMP-responsive element modulator (CREM) is reduced...
November 15, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27797910/islet-expressed-cxcl10-promotes-autoimmune-destruction-of-islet-iso-grafts-in-mice-with-type-1-diabetes
#13
Christine Bender, Selina Christen, Klaus Scholich, Monika Bayer, Josef M Pfeilschifter, Edith Hintermann, Urs Christen
Type 1 diabetes (T1D) results from the autoimmune destruction of insulin-producing β-cells in the pancreas. Thereby the chemokine CXC-motif ligand 10 (CXCL10) plays an important role in the recruitment of autoaggressive lymphocytes to the islets of Langerhans. Transplantation of isolated islets as a promising therapy of T1D has been hampered by early graft rejection. Here, we investigated the influence of CXCL10 on the autoimmune destruction of islet iso-grafts using RIP-LCMV mice expressing a lymphocytic choriomeningitis virus (LCMV) protein in the β-cells...
October 26, 2016: Diabetes
https://www.readbyqxmd.com/read/27795301/additive-protection-against-congenital-cmv-conferred-by-combined-gb-pp65-vaccination-using-a-lymphocytic-choriomeningitis-virus-lcmv-vector
#14
Mark R Schleiss, Ursula Berka, Elizabeth Watson, Mario Aistleithner, Bettina Kiefmann, Bastien Mangeat, Elizabeth C Swanson, Peter A Gillis, Nelmary Hernandez-Alvarado, Claudia Fernández-Alarcón, Jason C Zabeli, Daniel D Pinschewer, Anders Lilja, Michael Schwendinger, Farshad Guirakhoo, Thomas P Monath, Klaus Orlinger
Subunit vaccines for prevention of congenital cytomegalovirus (CMV) infection based on glycoprotein B (gB) and pp65 are in clinical trials, but it is unclear whether simultaneous vaccination with both antigens enhances protection. We undertook evaluation of a novel bivalent vaccine based on non-replicating lymphocytic choriomeningitis virus (rLCMV) vectors expressing a cytoplasmic tail-deleted gB (gB(dCt)), and full-length pp65 from human CMV in mice. Immunization with the gB(dCt) vector alone elicited a comparable gB-binding antibody response, and a superior neutralizing response, to that elicited by adjuvanted subunit gB...
October 26, 2016: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/27760221/impaired-subset-progression-and-polyfunctionality-of-t-cells-in-mice-exposed-to-methamphetamine-during-chronic-lcmv-infection
#15
Uma Sriram, Beth L Hill, Jonathan M Cenna, Larisa Gofman, Nicole C Fernandes, Bijayesh Haldar, Raghava Potula
Methamphetamine (METH) is a widely used psychostimulant that severely impacts the host's innate and adaptive immune systems and has profound immunological implications. T cells play a critical role in orchestrating immune responses. We have shown recently how chronic exposure to METH affects T cell activation using a murine model of lymphocytic choriomeningitis virus (LCMV) infection. Using the TriCOM (trinary state combinations) feature of GemStone™ to study the polyfunctionality of T cells, we have analyzed how METH affected the cytokine production pattern over the course of chronic LCMV infection...
2016: PloS One
https://www.readbyqxmd.com/read/27730627/irreversible-splenic-atrophy-following-chronic-lcmv-infection-is-associated-with-compromised-immunity-in-mice
#16
Achire N Mbanwi, Chao Wang, Kaoru Geddes, Dana J Philpott, Tania H Watts
Lymphocytic choriomeningitis virus clone 13 (LCMV13) infection of mice is a widely used model for investigating the mechanisms driving persistent viral infection in humans. LCMV13 disrupts splenic architecture early during infection, but this returns to normal within a few weeks. However, the long-term effects of LCMV13 infection on splenic structure have not been reported. Here we report that persistent infection with LCMV13 results in sustained splenic atrophy that persists for at least 500 days following infection, whereas infection with the acutely infecting LCMV Armstrong is associated with a return to pre-infection spleen weights...
October 11, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27721109/lymphocytic-choriomeningitis-ljungan-and-orthopoxvirus-seroconversions-in-patients-hospitalized-due-to-acute-puumala-hantavirus-infection
#17
Cristina Fevola, Kristian M Forbes, Satu Mäkelä, Niina Putkuri, Heidi C Hauffe, Hannimari Kallio-Kokko, Jukka Mustonen, Anne J Jääskeläinen, Antti Vaheri
BACKGROUND: The emergence and re-emergence of zoonotic and vector-borne diseases are increasing in Europe. Prominent rodent-borne zoonotic viruses include Puumala hantavirus (PUUV; the causative agent of nephropathia epidemica, NE), lymphocytic choriomeningitis virus (LCMV), and orthopoxviruses (OPV). In addition, Ljungan virus (LV) is considered a potentially zoonotic virus. OBJECTIVE: The aim of this study was to compare clinical picture between acute PUUV patients with and without additional rodent-borne viral infections, to investigate if concurrent infections influence disease severity...
October 4, 2016: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/27683954/novel-model-of-double-transgenic-mouse-results-in-autoimmune-diabetes-in-males
#18
Sylvie Chabot, Fernando Alvarez, Abdelaziz Amrani, Idriss Djilali-Saiah
Identifying the type of diabetogenic CD8(+) T cells that initiate autoimmune diabetes (AID) is a critical step in designing appropriate strategies for the early detection of beta cell-directed autoimmunity and its progression to diabetes. We generated a novel double transgenic (Tg) mouse model on the naturally diabetes resistant C57Bl/6 background, co-expressing two transgenes including a specific TCR anti-lymphocytic choriomeningitis virus nucleoprotein (LCMV-NP) carried by CD8(+) T cells and LCMV-NP (as neo-self antigen) expressed by pancreatic beta cells...
September 2016: Autoimmunity
https://www.readbyqxmd.com/read/27667772/t-cells-underlie-some-but-not-all-of-the-cerebellar-pathology-in-a-neonatal-rat-model-of-congenital-lymphocytic-choriomeningitis-virus-infection
#19
Hannah Klein, Glenda K Rabe, Bahri Karacay, Daniel J Bonthius
Lymphocytic choriomeningitis virus (LCMV) infection during pregnancy injures the human fetal brain. Neonatal rats inoculated with LCMV are an excellent model of congenital LCMV infection because they develop cerebellar injuries similar to those in humans. To evaluate the role of T-lymphocytes in LCMV-induced cerebellar pathology, congenitally athymic rats, deficient in T-lymphocytes were compared with euthymic rats. Peak viral titers and cellular targets of infection were similar, but viral clearance from astrocytes was impaired in the athymic rats...
September 25, 2016: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/27581982/residues-k465-and-g467-within-the-cytoplasmic-domain-of-gp2-play-a-critical-role-in-the-persistence-of-lymphocytic-choriomeningitis-virus-in-mice
#20
Masaharu Iwasaki, Cherie T Ng, Beatrice Cubitt, Juan C de la Torre
: Several arenaviruses, chiefly Lassa virus (LASV), cause hemorrhagic fever disease in humans and pose serious public health concerns in their regions of endemicity. Moreover, mounting evidence indicates that the worldwide-distributed prototypic arenavirus, lymphocytic choriomeningitis virus (LCMV), is a neglected human pathogen of clinical significance. We have documented that a recombinant LCMV containing the glycoprotein (GPC) gene of LASV within the backbone of the immunosuppressive clone 13 (Cl-13) variant of the Armstrong strain of LCMV (rCl-13/LASV-GPC) exhibited Cl-13-like growth properties in cultured cells, but in contrast to Cl-13, rCl-13/LASV-GPC was unable to establish persistence in immunocompetent adult mice, which prevented its use for some in vivo experiments...
November 15, 2016: Journal of Virology
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