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Herpes simplex virus and t cells

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https://www.readbyqxmd.com/read/29216507/chimeric-hcmv-hsv-1-and-%C3%AE-%C3%AE-134-5-oncolytic-herpes-simplex-virus-elicit-immune-mediated-antigliomal-effect-and-antitumor-memory
#1
Mohammed G Ghonime, Josh Jackson, Amish Shah, Justin Roth, Mao Li, Ute Saunders, Jennifer Coleman, G Yancey Gillespie, James M Markert, Kevin A Cassady
Malignant gliomas are the most common primary brain tumor and are characterized by rapid and highly invasive growth. Because of their poor prognosis, new therapeutic strategies are needed. Oncolytic virotherapy (OV) is a promising strategy for treating cancer that incorporates both direct viral replication mediated and immune mediated mechanisms to kill tumor cells. C134 is a next generation Δγ134.5 oHSV-1 with improved intratumoral viral replication. It remains safe in the CNS environment by inducing early IFN signaling which restricts its replication in non-malignant cells...
December 4, 2017: Translational Oncology
https://www.readbyqxmd.com/read/29213157/immunotherapy-and-gene-therapy-as-novel-treatments-for-cancer
#2
REVIEW
Martha Montserrat Rangel-Sosa, Estuardo Aguilar-Córdova, Augusto Rojas-Martínez
The immune system interacts closely with tumors during the disease development and progression to metastasis. The complex communication between the immune system and the tumor cells can prevent or promote tumor growth. New therapeutic approaches harnessing protective immunological mechanisms have recently shown very promising results. This is performed by blocking inhibitory signals or by activating immunological effector cells directly. Immune checkpoint blockade with monoclonal antibodies directed against the inhibitory immune receptors CTLA-4 and PD-1 has emerged as a successful treatment approach for patients with advanced melanoma...
September 30, 2017: Colombia Médica: CM
https://www.readbyqxmd.com/read/29206240/influence-of-an-immunodominant-herpes-simplex-virus-type-1-cd8-t-cell-epitope-on-the-target-hierarchy-and-function-of-subdominant-cd8-t-cells
#3
Benjamin R Treat, Sarah M Bidula, Srividya Ramachandran, Anthony J St Leger, Robert L Hendricks, Paul R Kinchington
Herpes simplex virus type 1 (HSV-1) latency in sensory ganglia such as trigeminal ganglia (TG) is associated with a persistent immune infiltrate that includes effector memory CD8+ T cells that can influence HSV-1 reactivation. In C57BL/6 mice, HSV-1 induces a highly skewed CD8+ T cell repertoire, in which half of CD8+ T cells (gB-CD8s) recognize a single epitope on glycoprotein B (gB498-505), while the remainder (non-gB-CD8s) recognize, in varying proportions, 19 subdominant epitopes on 12 viral proteins. The gB-CD8s remain functional in TG throughout latency, while non-gB-CD8s exhibit varying degrees of functional compromise...
December 4, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29186956/how-viruses-infiltrate-the-central-nervous-system
#4
A Michalicová, K Bhide, M Bhide, A Kováč
Central nervous system is protected by the blood-brain barrier, which represents a physical, metabolic and transport barrier and is considered to be a part of a highly dynamic system termed neurovascular unit. Several pathogens, among them viruses, are able to invade the brain. Traversal of viruses across the blood-brain barrier is an essential step for the invasion of the central nervous system and can occur by different mechanisms - by paracellular, transcellular and/or by "Trojan horse" pathway. Penetration of viruses to brain can lead to the blood-brain barrier dysfunction, including increased permeability, pleocytosis and encephalopathy...
2017: Acta Virologica
https://www.readbyqxmd.com/read/29186188/effect-of-age-on-chronic-inflammation-and-responsiveness-to-bacterial-and-viral-challenges
#5
Ingrid Elisia, Vivian Lam, Elyse Hofs, Michael Yu Li, Mariah Hay, Brandon Cho, Angela Brooks-Wilson, Miriam Rosin, Luke Bu, William Jia, Gerald Krystal
To identify reliable biomarkers of age-related changes in chronic inflammation and responsiveness to bacterial and viral challenges, we evaluated endogenous and ex vivo stimulated levels of 18 inflammatory markers, using whole blood collected in EDTA and sodium heparin tubes from 41 healthy volunteers, i.e., 11 men + 10 women aged 20-35 and 10 men + 10 women aged 50-77. These studies revealed significant differences in the levels of inflammatory markers when blood was collected in EDTA versus sodium heparin and age related differences in these biomarkers were confirmed with blood collected in EDTA from 120 healthy volunteers in 3 age categories, ie, 20 men + 20 women, aged 20-35, 36-49 and 50-77...
2017: PloS One
https://www.readbyqxmd.com/read/29179583/oncolytic-viruses-for-tumor-precision-imaging-and-radiotherapy
#6
Zi Jun Wu, Feng R Tang, Zhao-Wu Ma, Xiao-Chun Peng, Ying Xiang, Yanling Zhang, Jingbo Kang, Jiafu Ji, Xiao Q Liu, Xian-Wang Wang, Hong-Wu Xin, Bo X Ren
Dr. Peng et al invented the recombinant adenovirus expressing p53 (rAd-p53, Gendicine) for clinical tumor virotherapy in China in 2003, which is the first clinically approved gene therapy and tumor virotherapy drug in the world. An oncolytic herpes simplex virus expressing granulocyte-macrophage colony-stimulating factor (Talimogene laherparepvec, T-VEC) was approved for melanoma treatment in the United States in 2015. Since then, oncolytic viruses have been attracting more and more attention in the field of oncology, and may become novel significant modalities of tumor precision imaging and radiotherapy after further improvement...
November 27, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/29176979/us6-gene-deletion-in-herpes-simplex-virus-type-2-enhances-dendritic-cell-function-and-t-cell-activation
#7
Angello Retamal-Díaz, Kayla A Weiss, Eduardo I Tognarelli, Mariela Freire, Susan M Bueno, Betsy C Herold, William R Jacobs, Pablo A González
Herpes simplex virus (HSV) type 1 (HSV-1) and type 2 (HSV-2) produce lifelong infections that are associated with frequent asymptomatic or clinically apparent reactivation. Importantly, HSV express multiple virulence factors that negatively modulate innate and adaptive immune components. Notably, HSV interfere with dendritic cell (DC) viability and function, likely hindering the capacity of the host to mount effective immunity against these viruses. Recently, an HSV-2 virus that was deleted in glycoprotein D was engineered (designated ΔgD-2)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29157732/rnase-7-strongly-promotes-tlr9-mediated-dna-sensing-by-human-plasmacytoid-dendritic-cells
#8
V Kopfnagel, S Wagenknecht, J Harder, K Hofmann, M Kleine, A Buch, B Sodeik, T Werfel
Plasmacytoid dendritic cells (pDCs) were described to accumulate in the skin of patients with psoriasis and to be recruited into the dermis upon allergen challenge in atopic dermatitis. Importantly, activation of pDCs in the skin has been identified as important initiator of psoriasis development. RNase 7 is one of the major antimicrobial peptides (AMP) secreted by keratinocytes and is expressed in significantly higher amounts in lesional skin of patients with atopic dermatitis or psoriasis than in healthy individuals...
November 17, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29155164/a-new-promising-candidate-to-overcome-drug-resistant-herpes-simplex-virus-infections
#9
Elisabeth Zinser, Adalbert Krawczyk, Petra Mühl-Zürbes, Ulrich Aufderhorst, Lena Stich, Mirko Zaja, Stefan Strobl, Alexander Steinkasserer, Christiane Silke Heilingloh
Infections with Herpes simplex viruses (HSV) belong to the most common human diseases worldwide, resulting in symptoms ranging from painful, but commonly self-limiting lesions of the orofacial or genital tract to severe infections of the eye or life-threatening generalized infections. Frequent HSV-reactivations at the eye may lead to the development of herpetic stromal keratitis, which is one of the major causes of infectious blindness in developed countries. The vast majority of life-threatening generalized infections occur in immunocompromised individuals, such as transplant recipients or patients suffering from advanced human immunodeficiency virus (HIV) infection with concurrent HSV-reactivation...
November 15, 2017: Antiviral Research
https://www.readbyqxmd.com/read/29155096/patients-with-atopic-dermatitis-and-history-of-eczema-herpeticum-elicit-hsv-specific-type-2-immune-responses
#10
Stephan Traidl, Petra Kienlin, Gabriele Begemann, Lichen Jing, David M Koelle, Thomas Werfel, Lennart M Roesner
An increased type 2 and in parallel decreased type 1 T cell immune response to herpes simplex virus 1 may lead to the clinical phenotype of eczema herpeticum.
November 15, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29142130/effective-priming-of-hsv-specific-cd8-t-cells-in-vivo-does-not-require-infected-dendritic-cells
#11
Paul G Whitney, Christina Makhlouf, Beth MacLeod, Joel Z Ma, Elise Gressier, Marie Greyer, Katharina Hochheiser, Annabell Bachem, Ali Zaid, David Voehringer, William R Heath, Mayura V Wagle, Ian Parish, Tiffany A Russell, Stewart A Smith, David C Tscharke, Thomas Gebhardt, Sammy Bedoui
Resolution of virus infections depends on the priming of virus-specific CD8(+) T cells by dendritic cells (DC). While this process requires MHC class I-restricted antigen presentation by DC, the relative contribution to CD8(+) T cell priming by infected DC is less clear. We have addressed this question in the context of a peripheral infection with herpes simplex virus type 1 (HSV). Assessing the endogenous, polyclonal HSV-specific CD8(+) T cell response, we found that effective in vivo T cell priming depended on the presence of DC subsets specialized in cross-presentation while Langerhans cells and plasmacytoid DC were dispensable...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29114252/cd335-nkp46-t-cell-recruitment-to-the-bovine-upper-respiratory-tract-during-a-primary-bovine-herpesvirus-1-infection
#12
Rahwa A Osman, Philip John Griebel
Bovine natural killer (NK) cells were originally defined by the NK activation receptor CD335 [natural killer cell p46-related protein (NKp46)], but following the discovery of NKp46 expression on human T-cells, the definition of conventional bovine NK cells was modified to CD335(+)CD3(-) cells. Recently, a bovine T-cell population co-expressing CD335 was identified and these non-conventional T-cells were shown to produce interferon (IFN)-γ and share functional properties with both conventional NK cells and T-cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29093081/analysis-of-select-hsv-1-proteins-for-restriction-of-human-immunodeficiency-virus-type-1-the-hsv-1-gm-protein-potently-restricts-hiv-1-by-preventing-the-intracellular-transport-and-processing-of-env-gp160
#13
Sachith Polpitiya Arachchige, Wyatt Henke, Ankita Pramanik, Maria Kalamvoki, Edward B Stephens
Proteins encoded by viruses that impair or shutdown specific host cell functions during replication can be used as probes to identify potential proteins/pathways used in the replication of viruses from other families. We screened nine proteins from herpes simplex virus type 1 (HSV-1) for the ability to enhance or restrict human immunodeficiency virus type 1 (HIV-1) replication. We show that several HSV-1 proteins (glycoprotein M (gM), US3 and UL24) potently restricted the replication of HIV-1. Unlike UL24 and US3, which reduced viral protein synthesis, we observed that gM restriction of HIV-1 occurred through interference of the processing and transport of gp160, resulting in a significantly reduced level of mature gp120/gp41 released from cells...
November 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29057994/effects-of-herpes-simplex-virus-vectors-encoding-poreless-trpv1-or-protein-phosphatase-1%C3%AE-in-a-rat-cystitis-model-induced-by-hydrogen-peroxide
#14
S Takai, T Majima, B Reinhart, W F Goins, Y Funahashi, M Gotoh, P Tyagi, J C Glorioso, N Yoshimura
Enhanced afferent excitability is considered to be an important pathophysiological basis of interstitial cystitis/bladder pain syndrome (IC/BPS). In addition, transient receptor potential vanilloid-1 (TRPV1) receptors are known to be involved in afferent sensitization. Animals with hydrogen peroxide (HP)-induced cystitis have been used as a model exhibiting pathologic characteristics of chronic inflammatory condition of the bladder. This study investigated the effect of gene therapy with replication-defective herpes simplex virus (HSV) vectors encoding poreless TRPV1 (PL) or protein phosphatase 1 α (PP1α), a negative regulator of TRPV1, using a HP-induced rat model of cystitis...
October 20, 2017: Gene Therapy
https://www.readbyqxmd.com/read/29046357/structural-and-thermodynamic-analyses-reveal-critical-features-of-glycopeptide-recognition-by-the-human-pilr%C3%AE-immune-cell-receptor
#15
Atsushi Furukawa, Kosuke Kakita, Tomoki Yamada, Mikihiro Ishizuka, Jiro Sakamoto, Nanao Hatori, Naoyoshi Maeda, Fumina Ohsaka, Takashi Saitoh, Takao Nomura, Kimiko Kuroki, Hisanori Nambu, Hisashi Arase, Shigeki Matsunaga, Masahiro Anada, Toyoyuki Ose, Shunichi Hashimoto, Katsumi Maenaka
Before entering host cells, herpes simplex virus-1 (HSV-1) uses its envelope glycoprotein B (gB) to bind paired immunoglobulin-like type 2 receptor α (PILRα) on immune cells. PILRα belongs to the Siglec (sialic acid (SA)-binding immunoglobulin-like lectin)-like family, members of which bind SA. PILRα is the only Siglec member to recognize not only the sialylated O-linked sugar T antigen (sTn) but also its attached peptide region. We previously determined the crystal structure of PILRα complexed with the sTn-linked glycopeptide of gB, revealing the simultaneous recognition of sTn and peptide by the receptor...
October 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29034313/newly-characterized-murine-undifferentiated-sarcoma-models-sensitive-to-virotherapy-with-oncolytic-hsv-1-m002
#16
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
#17
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
#18
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
#19
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/novel-role-for-interleukin-17-in-enhancing-type-1-helper-t-cell-immunity-in-the-female-genital-tract-following-mucosal-herpes-simplex-virus-2-vaccination
#20
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 antiviral immunity against herpes simplex virus 2 (HSV-2) genital infection. However, the role of interleukin-17A (IL-17A) production by CD4(+) T cells in HSV-2 antiviral immunity is yet to be elucidated. Here we demonstrate that IL-17A plays an important role in enhancing antiviral T helper type 1 (Th1) responses in the female genital tract (FGT) and is essential for effective protection conferred by HSV-2 vaccination...
December 1, 2017: Journal of Virology
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