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Virus-specific T cell

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https://www.readbyqxmd.com/read/28931083/in-vivo-virulence-of-mhc-adapted-aids-virus-serially-passaged-through-mhc-mismatched-hosts
#1
Sayuri Seki, Takushi Nomura, Masako Nishizawa, Hiroyuki Yamamoto, Hiroshi Ishii, Saori Matsuoka, Teiichiro Shiino, Hironori Sato, Kazuta Mizuta, Hiromi Sakawaki, Tomoyuki Miura, Taeko K Naruse, Akinori Kimura, Tetsuro Matano
CD8+ T-cell responses exert strong suppressive pressure on HIV replication and select for viral escape mutations. Some of these major histocompatibility complex class I (MHC-I)-associated mutations result in reduction of in vitro viral replicative capacity. While these mutations can revert after viral transmission to MHC-I-disparate hosts, recent studies have suggested that these MHC-I-associated mutations accumulate in populations and make viruses less pathogenic in vitro. Here, we directly show an increase in the in vivo virulence of an MHC-I-adapted virus serially-passaged through MHC-I-mismatched hosts in a macaque AIDS model despite a reduction in in vitro viral fitness...
September 20, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28930702/gcamp-expression-in-retinal-ganglion-cells-characterized-using-a-low-cost-fundus-imaging-system
#2
Yao-Chuan Chang, Steven T Walston, Robert H Chow, James D Weiland
OBJECTIVE: Virus-transduced, intracellular-calcium indicators are effective reporters of neural activity, offering the advantage of cell-specific labeling. Due to the existence of an optimal time window for the expression of calcium indicators, a suitable tool for tracking GECI expression in vivo following transduction is highly desirable. APPROACH: We developed a noninvasive imaging approach based on a custom-modified, low-cost fundus viewing system that allowed us to monitor and characterize in vivo bright-field and fluorescence images of the mouse retina...
October 2017: Journal of Neural Engineering
https://www.readbyqxmd.com/read/28928736/selective-igm-deficiency-an-underestimated-primary-immunodeficiency
#3
REVIEW
Sudhir Gupta, Ankmalika Gupta
Although selective IgM deficiency (SIGMD) was described almost five decades ago, it was largely ignored as a primary immunodeficiency. SIGMD is defined as serum IgM levels below two SD of mean with normal serum IgG and IgA. It appears to be more common than originally realized. SIGMD is observed in both children and adults. Patients with SIGMD may be asymptomatic; however, approximately 80% of patients with SIGMD present with infections with bacteria, viruses, fungi, and protozoa. There is an increased frequency of allergic and autoimmune diseases in SIGMD...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28927824/cellular-therapy-for-multiple-pathogen-infections-after-hematopoietic-stem-cell-transplant
#4
REVIEW
Gaurav Sutrave, Emily Blyth, David J Gottlieb
Hematopoietic stem cell transplantation (HSCT) represents the only crative treatment option for many hematological conditions but results in a profound T-cell deficiency in the post-HSCT period. Infections account for a significant proportion of non-relapse morbidity and mortality, and infections with multiple organisms either simultaneously or at different times after transplant are common. Adoptive cellular therapy (ACT) with prophylactic or therapeutic infusion of donor derived or third-party, pathogen-specific T-cells represents a novel methodology to rapidly reconstitute T-cell mediated immunity in this context...
September 15, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28927823/t-cell-therapies-for-human-polyomavirus-diseases
#5
REVIEW
Sarah I Davies, Pawel Muranski
Rapid restoration of virus-specific T immunity via adoptive transfer of ex vivo generated T cells has been proven as a powerful therapy for patients with advanced cancers and refractory viral infections such as cytomegalovirus (CMV) and Epstein-Barr virus (EBV). BK virus (BKV), John Cunningham virus (JCV), and Merkel cell carcinoma virus (MCV) are the members of the rapidly growing human polyomavirus (hPyV) family that commonly infects most healthy humans. These viruses have a clearly established potential for causing severe end-organ damage or malignant transformation, especially in individuals with weakened immunity who are unable to mount or regain endogenous T-cell responses as a result of underlying leukemia or iatrogenic immunosuppression in autoimmunity, bone marrow and solid organ transplant settings...
September 15, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28926997/effects-of-cellular-methylation-on-transgene-expression-and-site-specific-integration-of-adeno-associated-virus
#6
Diptiman Chanda, Jonathan A Hensel, Jerome T Higgs, Rajat Grover, Niroop Kaza, Selvarangan Ponnazhagan
DNA methylation is a major epigenetic event that affects not only cellular gene expression but that also has the potential to influence bacterial and viral DNA in their host-dependent functions. Adeno-associated virus (AAV) genome contains a high degree of CpG sequences capable of methylation in its terminal repeat sequences, which are the sole elements retained in AAV-based vectors used in gene therapy. The present study determined the influence of methylation status of the host cell on wild type (wt) AAV integration and recombinant (r) AAV transgene expression in HeLa cells...
September 18, 2017: Genes
https://www.readbyqxmd.com/read/28925795/application-of-replication-defective-west-nile-virus-vector-to-non-flavivirus-vaccine-targets
#7
Maryann Giel-Moloney, Michael Vaine, Linong Zhang, Mark Parrington, Beata Gajewska, Thorsten U Vogel, Svetlana O Pougatcheva, Xiaochu Duan, Timothy Farrell, Irina Ustyugova, Sanjay Phogat, Harry Kleanthous, Konstantin V Pugachev
The RepliVaxvaccine platform(RV) is based on flavivirus genomes that are rationally attenuated by deletion. The self-limiting infection provided by RV has been demonstrated to be safe, highly immunogenic and efficacious for several vaccine candidates against flaviviruses. Here respiratory syncytial virus (RSV) F, influenza virus HA, and Simian Immunodeficiency virus (SIV) Env proteins were expressed in place of either prM-E or C-prM-E gene deletions of the West Nile (WN) genome. The resulting RV-RSV, -influenza and -SIV vaccine prototypes replicated efficiently in complementing helper cells expressing the WN structural proteins in trans...
September 19, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28925793/sequential-administration-of-mva-based-vaccines-and-pd-1-pd-l1-blocking-antibodies-confers-measurable-benefits-on-tumor-growth-and-survival-preclinical-studies-with-mva-%C3%AE-gal-and-mva-muc1-tg4010-in-a-murine-tumor-model
#8
Christelle Remy-Ziller, Christine Thioudellet, Julie Hortelano, Murielle Gantzer, Virginie Nourtier, Marie-Christine Claudepierre, Benoit Sansas, Xavier Préville, Kaïdre Bendjama, Eric Quemeneur, Karola Rittner
TG4010, a Modified Vaccinia virus Ankara (MVA) expressing human mucin1 (MUC1) has demonstrated clinical benefit for patients suffering from advanced non-small cell lung cancer (NSCLC) in combination with chemotherapy. To support its development, preclinical experiments were performed with either TG4010 or β-galactosidase-encoding MVA vector (MVA-βgal) in mice presenting tumors in the lung. Tumor growth was obtained after intravenous injection of CT26 murine colon cancer cells, engineered to express either MUC1 or βgal...
September 19, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28923683/a-hydrogel-matrix-prolongs-persistence-and-promotes-specific-localization-of-an-oncolytic-adenovirus-in-a-tumor-by-restricting-nonspecific-shedding-and-an-antiviral-immune-response
#9
Bo-Kyeong Jung, Eonju Oh, JinWoo Hong, Yunki Lee, Ki Dong Park, Chae-Ok Yun
Currently, intratumoral injection of an oncolytic adenovirus (Ad) is the conventional administration route in clinical trials. Nonetheless, the locally administered Ad disseminates to the surrounding nontarget tissues and has short biological activity due to immunogenicity of Ad, thus necessitating multiple injections to achieve a sufficient therapeutic index. In the present study, a tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-expressing oncolytic Ad (oAd-TRAIL) was encapsulated in a gelatin hydrogel (oAd-TRAIL/gel) to enhance and prolong antitumor efficacy of the virus after a single intratumoral injection...
September 7, 2017: Biomaterials
https://www.readbyqxmd.com/read/28923622/enzyme-linked-immunospot-assay-as-a-complementary-method-to-assess-and-monitor-cytomegalovirus-infection-in-kidney-transplant-recipients-on-pre-emptive-antiviral-therapy-a-single-center-experience
#10
E Favi, R Santangelo, S Iesari, M Morandi, G E Marcovecchio, E M Trecarichi, M P Salerno, M Ferraresso, F Citterio, J Romagnoli
BACKGROUND: Cytomegalovirus (CMV) disease represents a major cause of post-transplantation morbidity and mortality. To estimate the risk of infection and monitor response to antiviral therapy, current guidelines suggest combination of viral load monitoring with direct assessment of CMV-specific immune response. We used enzyme-linked immunospot (ELISpot) for the evaluation of CMV-specific T-cell response in kidney transplant recipients with CMV viremia and investigated how information gained could help manage CMV infection...
October 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28921955/characterization-of-site-specific-glycosylation-in-influenza-a-virus-hemagglutinin-produced-by-spodoptera-frugiperda-insect-cell-line
#11
Yanjun Liu, Shiaw-Lin Wu, Kerry Routenberg Love, William S Hancock
Influenza hemagglutinin is a surface glycoprotein related to virus invasion and host immune system response. Understanding site specific glycosylation of hemagglutinin will increase our knowledge about virus evolution and can improve the design and quality of vaccines. In our study, we used glycoproteomic analysis based on multienzyme digestion followed by LC tandem MS analysis to determine the glycosylation of Influenza hemagglutinin (H1/A/California/04/2009) using the following steps: PNGaseF treatment combined with trypsin or pepsin digestion were used to determine the glycosites and glycan occupancy...
September 18, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28918477/in-vitro-inhibition-of-hiv-1-replication-in-autologous-cd4-t-cells-indicates-viral-containment-by-multifactorial-mechanisms
#12
Ting Tu, Jianbo Zhan, Danlei Mou, Wei Li, Bin Su, Tong Zhang, Tao Li, Ning Li, Hao Wu, Cong Jin, Huabiao Chen
HIV-1-specific cytotoxic T lymphocytes (CTLs) and neutralizing antibodies (NAbs) are present during chronic infection, but the relative contributions of these effector mechanisms to viral containment remain unclear. Here, using an in vitro model involving autologous CD4(+) T cells, primary HIV-1 isolates, HIV-1-specific CTLs, and neutralizing monoclonal antibodies, we show that b12, a potent and broadly neutralizing monoclonal antibody to HIV-1, was able to block viral infection when preincubated with virus prior to infection, but was much less effective than CTLs at limiting virus replication when added to infected cell cultures...
September 15, 2017: Virologica Sinica
https://www.readbyqxmd.com/read/28917539/hemagglutinin-specific-cd4-t-cell-responses-following-2009-ph1n1-inactivated-split-vaccine-inoculation-in-humans
#13
Shuguang Tan, Shihong Zhang, Bin Wu, Yingze Zhao, Wei Zhang, Min Han, Ying Wu, Guoli Shi, Yingxia Liu, Jinghua Yan, Guizhen Wu, Hua Wang, George F Gao, Fengcai Zhu, William J Liu
Influenza A virus remains a major threat to public health, and the inactivated split-virus vaccine is the most prevalent vaccine used worldwide. However, our knowledge about cellular immune responses to the inactivated influenza virus vaccine and its correlation with humoral responses are yet limited, which has restricted our understanding of the vaccine's protective mechanisms. Herein, in two clinical trials, T-cell responses specific for both previously identified human leucocyte antigen (HLA)-I-restricted epitopes from influenza virus and hemagglutinin (HA) protein were longitudinally investigated before, during, and after a two-dose vaccination with the inactivated 2009 pandemic H1N1 (2009-pH1N1) vaccine...
September 13, 2017: Vaccine
https://www.readbyqxmd.com/read/28915405/hepatic-immunopathology-during-occult-hepacivirus-re-infection
#14
Cordelia Manickam, Amanda J Martinot, Rhianna A Jones, Valerie Varner, R Keith Reeves
Despite drug advances for Hepatitis C virus (HCV), re-infections remain prevalent in high-risk populations. Unfortunately, the role of preexisting viral immunity and how it modulates re-infection is unclear. GBV-B infection of common marmosets is a useful model to study tissue immune responses in hepacivirus infections, and in this study we re-challenged 4 animals after clearance of primary viremia. Although only low-to-absent viremia was observed following re-challenge, GBV-B viral RNA was detectable in liver, confirming re-infection...
September 12, 2017: Virology
https://www.readbyqxmd.com/read/28912369/customized-viral-immunotherapy-for-hpv-associated-cancer
#15
Matthew J Atherton, Kyle B Stephenson, Jonathan Pol, Fuan Wang, Charles Lefebvre, David F Stojdl, Jake K Nikota, Anna Dvorkin-Gheva, Andrew Nguyen, Lan Chen, Stephanie Johnson-Obaseki, Patrick J Villeneuve, Jean-Simon Diallo, Jim Dimitroulakos, Yonghong Wan, Brian D Lichty
The viral transforming proteins E6 and E7 make human papilloma virus positive (HPV+) malignancies an attractive target for cancer immunotherapy. However, therapeutic vaccination exerts limited efficacy in the setting of advanced disease. We designed a strategy to induce substantial specific immune responses against multiple epitopes of E6 and E7 proteins based on an attenuated transgene from HPV serotypes 16 and 18 that is incorporated into MG1-Maraba virotherapy (MG1-E6E7). Mutations introduced to the transgene abrogate the ability of E6 and E7 to perturb p53 and retinoblastoma, respectively, while maintaining the ability to invoke tumor-specific, multi-functional CD8+ T-cell responses...
September 14, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28910419/il-10-mediated-signals-act-as-a-switch-for-lymphoproliferation-in-human-t-cell-leukemia-virus-type-1-infection-by-activating-the-stat3-and-irf4-pathways
#16
Leila Sawada, Yoshiko Nagano, Atsuhiko Hasegawa, Hikari Kanai, Kai Nogami, Sayaka Ito, Tomoo Sato, Yoshihisa Yamano, Yuetsu Tanaka, Takao Masuda, Mari Kannagi
Human T-cell leukemia virus type-1 (HTLV-1) causes two distinct diseases, adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Since there are no disease-specific differences among HTLV-1 strains, the etiological mechanisms separating these respective lymphoproliferative and inflammatory diseases are not well understood. In this study, by using IL-2-dependent HTLV-1-infected T-cell lines (ILTs) established from patients with ATL and HAM/TSP, we demonstrate that the anti-inflammatory cytokine IL-10 and its downstream signals potentially act as a switch for proliferation in HTLV-1-infected cells...
September 14, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28910403/polymicrobial-sepsis-impairs-bystander-recruitment-of-effector-cells-to-infected-skin-despite-optimal-sensing-and-alarming-function-of-skin-resident-memory-cd8-t-cells
#17
Derek B Danahy, Scott M Anthony, Isaac J Jensen, Stacey M Hartwig, Qiang Shan, Hai-Hui Xue, John T Harty, Thomas S Griffith, Vladimir P Badovinac
Sepsis is a systemic infection that enhances host vulnerability to secondary infections normally controlled by T cells. Using CLP sepsis model, we observed that sepsis induces apoptosis of circulating memory CD8 T-cells (TCIRCM) and diminishes their effector functions, leading to impaired CD8 T-cell mediated protection to systemic pathogen re-infection. In the context of localized re-infections, tissue resident memory CD8 T-cells (TRM) provide robust protection in a variety of infectious models. TRM rapidly 'sense' infection in non-lymphoid tissues and 'alarm' the host by enhancing immune cell recruitment to the site of the infection to accelerate pathogen clearance...
September 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28904342/evolution-of-t-cell-responses-during-measles-virus-infection-and-rna-clearance
#18
Ashley N Nelson, Nicole Putnam, Debra Hauer, Victoria K Baxter, Robert J Adams, Diane E Griffin
Measles is an acute viral disease associated both with immune suppression and development of life-long immunity. Clearance of measles virus (MeV) involves rapid elimination of infectious virus during the rash followed by slow elimination of viral RNA. To characterize cellular immune responses during recovery, we analyzed the appearance, specificity and function of MeV-specific T cells for 6 months after respiratory infection of rhesus macaques with wild type MeV. IFN-γ and IL-17-producing cells specific for the hemagglutinin and nucleocapsid proteins appeared in circulation in multiple waves approximately 2-3, 8 and 18-24 weeks after infection...
September 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28904197/differential-inhibitory-receptor-expression-on-t-cells-delineates-functional-capacities-in-chronic-viral-infection
#19
Jeffrey E Teigler, Gennadiy Zelinskyy, Michael A Eller, Diane L Bolton, Mary Marovich, Alexander D Gordon, Aljawharah Alrubayyi, Galit Alter, Merlin L Robb, Jeffrey N Martin, Steven G Deeks, Nelson L Michael, Ulf Dittmer, Hendrik Streeck
Inhibitory receptors have been extensively described for their importance in regulating immune responses in chronic infections and cancers. Blocking the function of inhibitory receptors such as PD-1, CTLA-4, 2B4, Tim-3, and LAG-3 have shown promise for augmenting CD8 T cell activity and boosting pathogen-specific immunity. However, the prevalence of inhibitory receptors on CD4 T cells and their relative influence on CD4 T cell functionality in chronic HIV infection remains poorly described. We therefore determined and compared inhibitory receptor expression patterns of 2B4, CTLA-4, LAG-3, PD-1, and Tim-3 on virus-specific CD4 and CD8 T cells in relation to their functional T cell profile...
September 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28904195/vector-order-determines-protection-against-pathogenic-simian-immunodeficiency-virus-infection-in-a-triple-component-vaccine-by-balancing-cd4-and-cd8-t-cell-responses
#20
Ulrike Sauermann, Antonia Radaelli, Nicole Stolte-Leeb, Katharina Raue, Massimiliano Bissa, Carlo Zanotto, Michael Krawczak, Matthias Tenbusch, Klaus Überla, Brandon F Keele, Carlo De Giuli Morghen, Sieghart Sopper, Christiane Stahl-Hennig
An effective AIDS vaccine should elicit strong humoral and cellular immune responses while maintaining low levels of CD4(+) T cell activation to avoid the generation of target cells for viral infection. The present study investigated two prime-boost regimens, both starting vaccination with single cycle immunodeficiency virus, followed by two mucosal boosts either with recombinant adenovirus (rAd) or fowlpox virus (rFWPV) expressing SIVmac239 or SIVmac251 gag/pol and env genes, respectively. Finally, vectors were switched and systemically administered to the reciprocal group of animals...
September 13, 2017: Journal of Virology
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