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Herpes simplex virus and t cells

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https://www.readbyqxmd.com/read/29034313/newly-characterized-murine-undifferentiated-sarcoma-models-sensitive-to-virotherapy-with-oncolytic-hsv-1-m002
#1
Eric K Ring, Rong Li, Blake P Moore, Li Nan, Virginia M Kelly, Xiaosi Han, Elizabeth A Beierle, James M Markert, Jianmei W Leavenworth, G Yancey Gillespie, Gregory K Friedman
Despite advances in conventional chemotherapy, surgical techniques, and radiation, outcomes for patients with relapsed, refractory, or metastatic soft tissue sarcomas are dismal. Survivors often suffer from lasting morbidity from current treatments. New targeted therapies with less toxicity, such as those that harness the immune system, and immunocompetent murine sarcoma models to test these therapies are greatly needed. We characterized two new serendipitous murine models of undifferentiated sarcoma (SARC-28 and SARC-45) and tested their sensitivity to virotherapy with oncolytic herpes simplex virus 1 (HSV-1)...
December 15, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28992140/inflammation-induces-osteoclast-differentiation-from-peripheral-mononuclear-cells-in-chronic-kidney-disease-patients-crosstalk-between-the-immune-and-bone-systems
#2
Cesira Cafiero, Margherita Gigante, Giacomina Brunetti, Simona Simone, Nada Chaoul, Angela Oranger, Elena Ranieri, Silvia Colucci, Giovanni B Pertosa, Maria Grano, Loreto Gesualdo
Background: Inflammation and immune system alterations contribute to bone damage in many pathologies by inducing the differentiation of osteoclasts (OCs), the bone resorbing cells. This link is largely unexplored in chronic kidney disease (CKD) and haemodialysis (HD) patients, in which reduced renal function is accompanied by an increased inflammatory state and skeletal abnormality. Methods: We used ex vivo culture experiments to investigate the osteoclastogenic potential of peripheral blood mononuclear cells (PBMCs) of CKD and HD patients, focusing on immune cell subsets and inflammatory cytokines such as LIGHT and receptor activator of nuclear factor κB ligand (RANKL)...
July 21, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28981470/telomere-dynamics-in-immune-senescence-and-exhaustion-triggered-by-chronic-viral-infection
#3
REVIEW
Marcia Bellon, Christophe Nicot
The progressive loss of immunological memory during aging correlates with a reduced proliferative capacity and shortened telomeres of T cells. Growing evidence suggests that this phenotype is recapitulated during chronic viral infection. The antigenic volume imposed by persistent and latent viruses exposes the immune system to unique challenges that lead to host T-cell exhaustion, characterized by impaired T-cell functions. These dysfunctional memory T cells lack telomerase, the protein capable of extending and stabilizing chromosome ends, imposing constraints on telomere dynamics...
October 5, 2017: Viruses
https://www.readbyqxmd.com/read/28958807/biologic-interactions-between-hsv-2-and-hiv-1-and-possible-implications-for-hsv-vaccine-development
#4
Joshua T Schiffer, Sami L Gottlieb
Development of a safe and effective vaccine against herpes simplex virus type 2 (HSV-2) has the potential to limit the global burden of HSV-2 infection and disease, including genital ulcer disease and neonatal herpes, and is a global sexual and reproductive health priority. Another important potential benefit of an HSV-2 vaccine would be to decrease HIV infections, as HSV-2 increases the risk of HIV-1 acquisition several-fold. Acute and chronic HSV-2 infection creates ulcerations and draws dendritic cells and activated CD4+ T cells into genital mucosa...
September 25, 2017: Vaccine
https://www.readbyqxmd.com/read/28956763/a-novel-role-for-il-17-in-enhancing-type-1-helper-t-cell-immunity-in-the-female-genital-tract-following-mucosal-hsv-2-vaccination
#5
Puja Bagri, Varun C Anipindi, Philip V Nguyen, Danielle Vitali, Martin R Stämpfli, Charu Kaushic
It is well established that interferon-gamma (IFN-γ) production by CD4(+) T cells is critical for anti-viral immunity against herpes simplex virus type 2 (HSV-2) genital infection. However, the role of interleukin-17A (IL-17A) production by CD4(+) T cells in HSV-2 anti-viral immunity is yet to be elucidated. Here, we demonstrate that IL-17A plays an important role in enhancing anti-viral T helper type 1 (Th1) responses in the female genital tract (FGT), and is essential for effective protection conferred by HSV-2 vaccination...
September 27, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28891812/herpes-simplex-virus-1-evasion-of-cd8-t-cell-accumulation-contributes-to-viral-encephalitis
#6
Naoto Koyanagi, Takahiko Imai, Keiko Shindo, Ayuko Sato, Wataru Fujii, Takeshi Ichinohe, Naoki Takemura, Shigeru Kakuta, Satoshi Uematsu, Hiroshi Kiyono, Yuhei Maruzuru, Jun Arii, Akihisa Kato, Yasushi Kawaguchi
Herpes simplex virus-1 (HSV-1) is the most common cause of sporadic viral encephalitis, which can be lethal or result in severe neurological defects even with antiviral therapy. While HSV-1 causes encephalitis in spite of HSV-1-specific humoral and cellular immunity, the mechanism by which HSV-1 evades the immune system in the central nervous system (CNS) remains unknown. Here we describe a strategy by which HSV-1 avoids immune targeting in the CNS. The HSV-1 UL13 kinase promotes evasion of HSV-1-specific CD8+ T cell accumulation in infection sites by downregulating expression of the CD8+ T cell attractant chemokine CXCL9 in the CNS of infected mice, leading to increased HSV-1 mortality due to encephalitis...
October 2, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28886376/converting-cold-into-hot-tumors-by-combining-immunotherapies
#7
John B A G Haanen
In a small phase Ib study in this issue of Cell, Ribas et al. report that the combination of intralesional injection of a modified human herpes simplex virus and systemic anti-PD-1 treatment resulted in a 62% response rate in patients with metastatic melanoma, accompanied by enhanced T cell infiltration in virus-injected lesions.
September 7, 2017: Cell
https://www.readbyqxmd.com/read/28853921/human-genetic-determinants-of-viral-diseases
#8
Adam D Kenney, James A Dowdle, Leonia Bozzacco, Temet M McMichael, Corine St Gelais, Amanda R Panfil, Yan Sun, Larry S Schlesinger, Matthew Z Anderson, Patrick L Green, Carolina B López, Brad R Rosenberg, Li Wu, Jacob S Yount
Much progress has been made in the identification of specific human gene variants that contribute to enhanced susceptibility or resistance to viral diseases. Herein we review multiple discoveries made with genome-wide or candidate gene approaches that have revealed significant insights into virus-host interactions. Genetic factors that have been identified include genes encoding virus receptors, receptor-modifying enzymes, and a wide variety of innate and adaptive immunity-related proteins. We discuss a range of pathogenic viruses, including influenza virus, respiratory syncytial virus, human immunodeficiency virus, human T cell leukemia virus, human papilloma virus, hepatitis B and C viruses, herpes simplex virus, norovirus, rotavirus, parvovirus, and Epstein-Barr virus...
August 30, 2017: Annual Review of Genetics
https://www.readbyqxmd.com/read/28841444/herpes-simplex-virus-1-infection-of-t-cells-causes-vp11-12-dependent-phosphorylation-and-degradation-of-the-cellular-protein-dok-2
#9
Soumia Lahmidi, Ulrike Strunk, James R Smiley, Angela Pearson, Pascale Duplay
Previous studies have shown that HSV-1 infection of lymphocytes induces the tyrosine phosphorylation of several proteins that might correspond to viral or host proteins. VP11/12, a viral tegument protein, is the major HSV-induced tyrosine phosphorylated protein identified thus far. In this report, we demonstrated that the cellular adaptor proteins Dok-2 and Dok-1 are tyrosine phosphorylated upon HSV-1 infection. In addition, HSV-1 induced the selective degradation of Dok-2. Finally, we provide evidence that Dok-2 interacts with VP11/12, and that HSV-induced tyrosine phosphorylation and degradation of Dok-2 require VP11/12...
November 2017: Virology
https://www.readbyqxmd.com/read/28810147/macrophage-polarization-contributes-to-glioblastoma-eradication-by-combination-immunovirotherapy-and-immune-checkpoint-blockade
#10
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
#11
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...
September 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
#12
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 (DCs) to present viral antigens on MHC class I after infection with a mutant herpes simplex virus 1 (HSV-1-Δ34.5), lacking infected cell protein 34.5 (ICP34.5), when compared to its parental HSV-1 strain...
October 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
#13
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
#14
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
#15
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
#16
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
#17
Arcadio Agudelo-Hernandez, Yue Chen, Arlene Bullotta, William G Buchanan, Cynthia R Klamar-Blain, Luann Borowski, Sharon A Riddler, Charles R Rinaldo, Bernard J C Macatangay
OBJECTIVE: We evaluated the subclinical shedding of six different herpesviruses in antiretroviral drug-treated HIV-positive [HIV(+)] 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-negative [HIV (-)] MSM from the Multicenter AIDS Cohort Study at four 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...
September 24, 2017: AIDS
https://www.readbyqxmd.com/read/28722019/sustained-accumulation-of-antigen-presenting-cells-after-infection-promotes-local-t-cell-immunity
#18
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
#19
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
#20
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
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