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Herpes simplex virus and t cells

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https://www.readbyqxmd.com/read/28810147/macrophage-polarization-contributes-to-glioblastoma-eradication-by-combination-immunovirotherapy-and-immune-checkpoint-blockade
#1
Dipongkor Saha, Robert L Martuza, Samuel D Rabkin
Glioblastoma is an immunosuppressive, fatal brain cancer that contains glioblastoma stem-like cells (GSCs). Oncolytic herpes simplex virus (oHSV) selectively replicates in cancer cells while inducing anti-tumor immunity. oHSV G47Δ expressing murine IL-12 (G47Δ-mIL12), antibodies to immune checkpoints (CTLA-4, PD-1, PD-L1), or dual combinations modestly extended survival of a mouse glioma model. However, the triple combination of anti-CTLA-4, anti-PD-1, and G47Δ-mIL12 cured most mice in two glioma models...
August 14, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28809154/interaction-between-herpesvirus-entry-mediator-and-hsv-2-glycoproteins-mediates-hiv-1-entry-of-hsv-2-infected-epithelial-cells
#2
Kai Hu, Siyi He, Juhua Xiao, Mei Li, Sukun Luo, Mudan Zhang, Qinxue Hu
Herpes simplex virus type 2 (HSV-2) increases human immunodeficiency virus type 1 (HIV-1) acquisition and transmission via unclear mechanisms. Herpesvirus entry mediator (HVEM), an HSV-2 entry receptor, is highly expressed on HIV-1 target cells (CD4+ T cells) and may be incorporated into HIV-1 virions, while HSV-2 glycoproteins can be present on the infected cell surface. Since HVEM-gD interaction together with gB/gH/gL is essential for HSV-2 entry, HVEM-bearing HIV-1 (HIV-1/HVEM) may enter HSV-2-infected cells through such interactions...
August 15, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28771693/herpes-simplex-virus-1-interferes-with-autophagy-of-murine-dendritic-cells-and-impairs-their-ability-to-stimulate-cd8-t-lymphocytes
#3
Ramachandramouli Budida, Metodi V Stankov, Katinka Döhner, Anna Buch, Diana Panayotova-Dimitrova, Kim A Tappe, Anja Pohlmann, Beate Sodeik, Georg M N Behrens
The MHC class I presentation is responsible for the presentation of viral proteins to CD8(+) T lymphocytes and mainly depends on the classical antigen processing pathway. Recently, a second pathway involving autophagy has been implicated in this process. Here, we show an increase in the capacity of murine dendritic cells to present viral antigens on MHC class I after infection with a mutant herpes simplex virus 1 (HSV-1-Δ34.5), lacking ICP34.5, when compared to its parental HSV-1 strain. The ICP34.5 protein counteracts host cell translational arrest and suppresses macroautophagy, and the lack of this protein resulted in a low viral protein abundance, which was processed and presented in an efficient way...
August 3, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28770166/genomic-signature-of-the-natural-oncolytic-herpes-simplex-virus-hf10-and-its-therapeutic-role-in-preclinical-and-clinical-trials
#4
REVIEW
Ibrahim Ragab Eissa, Yoshinori Naoe, Itzel Bustos-Villalobos, Toru Ichinose, Maki Tanaka, Wu Zhiwen, Nobuaki Mukoyama, Taishi Morimoto, Noriyuki Miyajima, Hasegawa Hitoki, Seiji Sumigama, Branko Aleksic, Yasuhiro Kodera, Hideki Kasuya
Oncolytic viruses (OVs) are opening new possibilities in cancer therapy with their unique mechanism of selective replication within tumor cells and triggering of antitumor immune responses. HF10 is an oncolytic herpes simplex virus-1 with a unique genomic structure that has non-engineered deletions and insertions accompanied by frame-shift mutations, in contrast to the majority of engineered OVs. At the genetic level, HF10 naturally lacks the expression of UL43, UL49.5, UL55, UL56, and latency-associated transcripts, and overexpresses UL53 and UL54...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28763115/design-synthesis-and-the-biological-evaluation-of-a-new-series-of-acyclic-1-2-3-triazole-nucleosides
#5
Iwona E Głowacka, Graciela Andrei, Dominique Schols, Robert Snoeck, Katarzyna Gawron
A new strategy for the synthesis of N(3) -benzoylated- and N(3) -benzylated N(1) -propargylquinazoline-2,4-diones 30a-d and 31a-d from isatoic anhydride 41 is reported. The alkynes 30a-d and 31a-d were applied in the 1,3-dipolar cycloadditions with azides 27 and 28 to synthesize acyclic 1,2,3-triazole nucleosides. The obtained alkynes and 1,2,3-triazole were evaluated for antiviral activity against a broad range of DNA and RNA viruses. The alkyne 30d showed activity against adenovirus-2 (EC50  = 8.3 μM), while compounds 37a and 37d were also active toward herpes simplex virus-1 wild-type and thymidine kinase deficient (HSV-1 TK(-) ) strains (EC50 values in the range of 4...
August 1, 2017: Archiv der Pharmazie
https://www.readbyqxmd.com/read/28748667/a-model-of-genital-herpes-simplex-virus-type-1-infection-in-rhesus-macaques
#6
Meropi Aravantinou, Ines Frank, Geraldine Arrode-Bruses, Moriah Szpara, Brooke Grasperge, James Blanchard, Agegnehu Gettie, Nina Derby, Elena Martinelli
BACKGROUND: Although HSV-2 is the major cause of genital lesions, HSV-1 accounts for half of new cases in developed countries. METHODS: Three healthy SHIV-SF162P3-infected Indian rhesus macaques were inoculated with 4×10(8) pfu of HSV-1 twice, with the second inoculation performed after the vaginal mucosa was gently abraded with a cytobrush. RESULTS: HSV-1 DNA was detected in vaginal swabs 5 days after the second but not the first inoculation in all three macaques...
August 2017: Journal of Medical Primatology
https://www.readbyqxmd.com/read/28745327/seminal-vesicle-fluid-increases-the-efficacy-of-intravaginal-hsv-2-vaccination
#7
A Varese, F Remes Lenicov, M Gonzalez Prinz, A Paletta, G Ernst, C Maeto, A Merlotti, J Sabatte, S Símula, M P Holgado, E Dantas, J Geffner, A Ceballos
Once considered merely as a vehicle for spermatozoa, it is now clear that seminal plasma (SP) induces a variety of biological actions on the female reproductive tissues able to modulate the immune response against paternal antigens. To our knowledge, the influence of SP on the immune response against sexually transmitted pathogens has not been yet evaluated. We here analyzed whether the seminal vesicle fluid (SVF), which contributes almost 60% of the SP volume in mice, could modulate the immune response against herpes simplex virus type 2 (HSV-2)...
July 26, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28723708/subclinical-herpesvirus-shedding-among-hiv-1-infected-men-on-antiretroviral-therapy
#8
Arcadio Agudelo-Hernandez, Yue Chen, Arlene Bullotta, William G Buchanan, Cynthia R Klamar-Blain, Luann Borowski, Sharon A Riddler, Charles R Rinaldo, Bernard Jc Macatangay
DESIGN: We evaluated the subclinical shedding of 6 different herpesviruses in antiretroviral drug-treated HIV(+) men who have sex with men (MSM), and determined how this is associated with markers of inflammation and immune activation. METHODS: We obtained blood, semen, throat washing, urine, and stool from 15 antiretroviral-treated HIV-1-infected MSM with CD4 T cell reconstitution, and 12 age-matched HIV(-) MSM from the Multicenter AIDS Cohort Study at 4 timepoints over 24 weeks to measure DNA levels of cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus 1 and 2, human herpesvirus 6 (HHV6), and HHV8...
July 18, 2017: AIDS
https://www.readbyqxmd.com/read/28722019/sustained-accumulation-of-antigen-presenting-cells-after-infection-promotes-local-t-cell-immunity
#9
Nicholas Collins, Katharina Hochheiser, Francis R Carbone, Thomas Gebhardt
Antigen-presenting cells (APC) such as dendritic cells (DC) and macrophages are critical for T cell-mediated immunity. While it is established that memory T cells accumulate and persist in peripheral tissues after the resolution of infection, whether this is also the case for APC remains unclear. Here, we report that CCR2-dependent cells infiltrate skin during acute infection with herpes simplex virus (HSV)-1 and subsequently give rise to localized populations of dendritic cells and macrophages. These APC are found at elevated numbers at sites of resolved infection or inflammation compared to unaffected regions of skin...
July 19, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28720717/sting-is-an-essential-mediator-of-the-ku70-mediated-production-of-ifn-%C3%AE-1-in-response-to-exogenous-dna
#10
Hongyan Sui, Ming Zhou, Hiromi Imamichi, Xiaoli Jiao, Brad T Sherman, H Clifford Lane, Tomozumi Imamichi
We previously identified Ku70, a subunit of a DNA repair protein complex, as a cytosolic DNA sensor that induces the production of interferon-λ1 (IFN-λ1) by human primary cells and cell lines. IFN-λ1 is a type III IFN and has similar antiviral activity to that of the type I IFNs (IFN-α and IFN-β). We observed that human embryonic kidney (HEK) 293T cells, which are deficient in the innate immune adaptor protein STING (stimulator of IFN genes), did not produce IFN-λ1 in response to DNA unless they were reconstituted with STING...
July 18, 2017: Science Signaling
https://www.readbyqxmd.com/read/28710334/stem-cell-released-oncolytic-herpes-simplex-virus-has-therapeutic-efficacy-in-brain-metastatic-melanomas
#11
Wanlu Du, Ivan Seah, Oumaima Bougazzoul, GiHun Choi, Katrina Meeth, Marcus W Bosenberg, Hiroaki Wakimoto, David Fisher, Khalid Shah
The recent Food and Drug Administration approval of immunogenic oncolytic virus (OV) has opened a new era in the treatment of advanced melanoma; however, approximately 50% of patients with melanoma develop brain metastasis, and currently there are no beneficial treatment options for such patients. To model the progression of metastases seen in patients and to overcome the hurdles of systemic delivery of OV, we developed melanoma brain metastasis models in immunocompromised and immunocompetent mice, and tested the fate and efficacy of oncolytic herpes simplex virus (oHSV)-armed mesenchymal stem cells (MSCs)...
July 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28701399/selective-expression-of-ccr10-and-cxcr3-by-circulating-human-hsv-specific-cd8-t-cells
#12
Michael T Hensel, Tao Peng, Anqi Cheng, Stephen C De Rosa, Anna Wald, Kerry J Laing, Lichen Jing, Lichun Dong, Amalia S Magaret, David M Koelle
Herpes simplex virus type (HSV) infection is restricted to epithelial cells and neurons and is controlled by CD8 T-cells. These cells both traffic to epithelial sites of recurrent lytic infection and to ganglia, and persist at the dermal-epidermal junction for up to 12 weeks after lesion resolution. We previously showed that cutaneous lymphocyte-associated antigen (CLA), a functional E-selectin ligand (ESL), is selectively expressed on circulating HSV-2-specific CD8 T-cells. CLA/ESL mediates adhesion of T-cells to inflamed vascular endothelium...
July 12, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28680648/treating-refractory-post-herpetic-anti-n-methyl-d-aspartate-receptor-encephalitis-with-rituximab
#13
Christine Strippel, Constanze Mönig, Kristin S Golombeck, Andre Dik, Kathrin Bönte, Stjepana Kovac, Andreas Schulte-Mecklenbeck, Heinz Wiendl, Sven G Meuth, Andreas Johnen, Catharina C Gross, Nico Melzer
Herpes simplex virus-1 has been identified as the trigger factor in certain cases of NMDA-receptor autoimmune encephalitis. We report on a 67-year-old female patient, who was severely affected by post-herpetic NMDA-receptor autoimmune encephalitis. Her symptoms did not improve under methylprednisolone pulse therapy and plasma exchange under acyclovir prophylaxis. She received protein A immunoadsorption and a long-term immunosuppression with rituximab. Under treatment, activated T-cells as well as B- and plasma cells decreased in peripheral blood and cerebrospinal fluid, and anti-NMDA-R IgG titers in serum and cerebrospinal fluid declined with near complete cessation of intrathecal autoantibody synthesis...
July 2017: Oxford Medical Case Reports
https://www.readbyqxmd.com/read/28652233/potent-inhibition-of-hiv-1-replication-in-resting-cd4-t-cells-by-resveratrol-and-pterostilbene
#14
Chi N Chan, Benjamin Trinité, David N Levy
HIV-1 infection of resting CD4 T cells plays a crucial and numerically dominant role during virus transmission at mucosal sites and during subsequent acute replication and T cell depletion. Resveratrol and pterostilbene are plant stilbenoids associated with several health promoting benefits. Resveratrol has been shown to inhibit replication of several viruses, including herpes simplex 1 and 2, papillomaviruses, SARS virus and influenza virus. Alone, resveratrol does not inhibit HIV-1 infection of activated T cells, but it does synergize with nucleoside reverse transcriptase inhibitors in these cells to inhibit reverse transcription...
June 26, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28650722/optimized-dna-vaccine-enhanced-by-adjuvant-il28b-induces-protective-immune-responses-against-herpes-simplex-virus-type-2-in-mice
#15
Yan Zhou, Ziyan Wang, Yongqing Xu, Zeqiang Zhang, Rui Hua, Wei Liu, Chunlai Jiang, Yan Chen, Wenying Yang, Wei Kong
Antigen-specific immune responses determine the efficacy of herpes simplex virus type 2 (HSV-2) vaccines. To optimize the immunogenicity of the antigen gD2, we developed the gD2ΔUL25 DNA vaccine encoding HSV-2 glycoprotein D and UL25 gene encoding viral capsid vertex proteins in this study. The gD2 and gD2ΔUL25 DNA vaccines were compared with formalin-inactivated HSV-2 (FI-HSV-2), and results showed a greater protective immune response induced by gD2ΔUL25 than by gD2. Therefore, gD2ΔUL25 was chosen to evaluate further using the IL28B adjuvant...
June 26, 2017: Viral Immunology
https://www.readbyqxmd.com/read/28647211/tubuloreticular-inclusions-in-peritubular-capillaries-of-renal-allografts
#16
Jee Youn Lee, Seung Hwan Song, Yu Seun Kim, Beom Jin Lim, Soon Il Kim, Myoung Soo Kim, Hyeon Joo Jeong
BACKGROUND: Tubuloreticular inclusions (TRIs) are anastomosing networks of microtubules that are frequently found in autoimmune diseases and viral infections. In renal allografts, TRIs have been reported in glomerular endothelial cells in association with viral infections and donor specific antibodies (DSAs), but their presence in peritubular capillaries has not been explored. METHODS: We collected seven cases with TRIs out of 148 consecutive renal allograft biopsies taken from Dec...
June 6, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28645309/herpes-simplex-virus-1-infects-the-olfactory-bulb-shortly-following-ocular-infection-and-exhibits-a-long-term-inflammatory-profile-in-the-form-of-effector-and-hsv-1-specific-t-cells
#17
Chandra M Menendez, Daniel J J Carr
BACKGROUND: Herpes simplex virus 1 (HSV-1) infection can result in a life-threatening condition known as herpes simplex encephalitis (HSE). Trafficking patterns by which the virus reaches the central nervous system (CNS) following ocular infection are unresolved. We evaluated early viral dissemination pathways following ocular infection that involve trafficking to the olfactory bulb (OB). Additionally, we have characterized the capacity of HSV-1 to establish latency within OB tissue and profiled the local T lymphocyte response over the course of the acute infection into latency...
June 23, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28642110/pedf-plus-dha-modulate-inflammation-and-stimulate-nerve-regeneration-after-hsv-1-infection
#18
Jiucheng He, Donna Neumann, Azucena Kakazu, Thang Luong Pham, Farhana Musarrat, M Soledad Cortina, Haydee E P Bazan
Herpes simplex virus type-1 (HSV-1) infection leads to impaired corneal sensation and, in severe cases, to corneal ulceration, melting and perforation. Here, we explore the potential therapeutic action of pigment epithelial-derived factor (PEDF) plus docosahexaenoic acid (DHA) on corneal inflammation and nerve regeneration following HSV-1 infection. Rabbits inoculated with 100,000 PFU/eye of HSV-1 strain 17Syn+ were treated with PEDF + DHA or vehicle. PEDF + DHA treatment resulted in a biphasic immune response with stronger infiltration of CD4+T cells, neutrophils and macrophages at 7-days post-treatment (p...
August 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28639215/regulation-of-t-type-ca-2-channel-expression-by-herpes-simplex-virus-1-infection-in-sensory-like-nd7-cells
#19
Qiaojuan Zhang, Shao-Chung Hsia, Miguel Martin-Caraballo
Infection of sensory neurons by herpes simplex virus (HSV)-1 disrupts electrical excitability, altering pain sensory transmission. Because of their low threshold for activation, functional expression of T-type Ca(2+) channels regulates various cell functions, including neuronal excitability and neuronal communication. In this study, we have tested the effect of HSV-1 infection on the functional expression of T-type Ca(2+) channels in differentiated ND7-23 sensory-like neurons. Voltage-gated Ca(2+) currents were measured using whole cell patch clamp recordings in differentiated ND7-23 neurons under various culture conditions...
June 21, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28611307/review-oncolytic-virotherapy-updates-and-future-directions
#20
REVIEW
Christos Fountzilas, Sukeshi Patel, Devalingam Mahalingam
Oncolytic viruses (OVs) are viral strains that can infect and kill malignant cells while spare their normal counterparts. OVs can access cells through binding to receptors on their surface or through fusion with the plasma membrane and establish a lytic cycle in tumors, while leaving normal tissue essentially unharmed. Multiple viruses have been investigated in humans for the past century. IMLYGIC™ (T-VEC/Talimogene Laherparepvec), a genetically engineered Herpes Simplex Virus, is the first OV approved for use in the United States and the European Union for patients with locally advanced or non-resectable melanoma...
May 31, 2017: Oncotarget
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