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Herpes simplex virus and t cells

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https://www.readbyqxmd.com/read/28539588/cooperation-of-oncolytic-herpes-virotherapy-and-pd-1-blockade-in-murine-rhabdomyosarcoma-models
#1
Chun-Yu Chen, Pin-Yi Wang, Brian Hutzen, Les Sprague, Hayley M Swain, Julia K Love, Joseph R Stanek, Louis Boon, Joe Conner, Timothy P Cripe
Oncolytic virotherapy is an effective immunotherapeutic approach for cancer treatment via a multistep process including direct tumor cell lysis, induction of cytotoxic or apoptosis-sensitizing cytokines and promotion of antitumor T cell responses. Solid tumors limit the effectiveness of immunotherapeutics in diverse ways such as secretion of immunosuppressive cytokines and expression of immune inhibitory ligands to inhibit antitumor T cell function. Blocking programmed cell death protein (PD)-1 signaling, which mediates T cell suppression via engagement of its inhibitory ligands, PD-L1 or PD-L2, is of particular interest due to recent successes in many types of cancer...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28522585/herpes-simplex-virus-glycoprotein-d-targets-a-specific-dendritic-cell-subset-and-improves-the-performance-of-vaccines-to-human-papillomavirus-associated-tumors
#2
Bruna F M M Porchia, Ana Carolina R Moreno, Rodrigo N Ramos, Mariana O Diniz, Laís Helena T M de Andrade, Daniela S Rosa, José Alexandre M Barbuto, Silvia B Boscardin, Luís Carlos S Ferreira
Cervical cancer is a major public health problem and one of the leading causes of cancer deaths in women. Virtually all cases of cervical cancer, as well as a growing share of anal and head/neck tumors, are associated with human papillomavirus (HPV) infection. Despite the effectiveness, the available prophylactic vaccines do not benefit women with cervical lesions or cancer. Therefore, the search of new immunotherapeutic approaches to treat HPV-induced tumors is still a priority. The present study characterizes a therapeutic antitumor vaccine based on the genetic fusion of the Herpes simplex virus-1 (HSV-1) glycoprotein D (gD) with the E7 oncoprotein from HPV-16 (gDE7)...
May 18, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28507788/adaptive-t-cell-responses-induced-by-oncolytic-herpes-simplex-virus-granulocyte-macrophage-colony-stimulating-factor-therapy-expanded-by-dendritic-cell-and-cytokine-induced-killer-cell-adoptive-therapy
#3
Jun Ren, William R Gwin, Xinna Zhou, Xiaoli Wang, Hongyan Huang, Ni Jiang, Lei Zhou, Pankaj Agarwal, Amy Hobeika, Erika Crosby, Zachary C Hartman, Michael A Morse, Kevin H Eng, H Kim Lyerly
Purpose: Although local oncolytic viral therapy (OVT) may enhance tumor lysis, antigen release, and adaptive immune responses, systemic antitumor responses post-therapy are limited. Adoptive immunotherapy with autologous dendritic cells (DC) and cytokine-induced killer cells (DC-CIK) synergizes with systemic therapies. We hypothesized that OVT with Herpes Simplex Virus-granulocyte macrophage-colony-stimulating factor (HSV-GM-CSF) would induce adaptive T cell responses that could be expanded systemically with sequential DC-CIK therapy...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28490594/dok-1-and-dok-2-are-required-to-maintain-herpes-simplex-virus-1-specific-cd8-t-cells-in-a-murine-model-of-ocular-infection
#4
Soumia Lahmidi, Mitra Yousefi, Slimane Dridi, Pascale Duplay, Angela Pearson
Dok-1 and Dok-2 negatively regulate responses downstream of several immune receptors in lymphoid and myeloid cells. Recent evidence showed that Dok proteins are essential in the formation of memory CD8(+) T cells to an exogenous epitope expressed by vaccinia virus; however, the importance of Dok-1 and Dok-2 in the control of viral infection is unknown. Herein, we investigated the role of Dok proteins in modulating the immune response against herpes simplex virus 1 (HSV-1) in a mouse model of ocular infection...
May 10, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28490589/roles-of-m1-and-m2-macrophages-in-herpes-simplex-virus-1-infectivity
#5
Dhong Hyun Lee, Homayon Ghiasi
Macrophages are the predominant infiltrate in the corneas of mice that have been ocularly infected withHSV-1. However, very little is known concerning the relative roles of M1 (classically activated or polarized) and M2 (alternatively activated or polarized) macrophages in ocular HSV-1 infection. To better understand these relationships, we assessed the impact of directed M1 or M2 activation of RAW264.7 macrophages and peritoneal macrophages (PM) on subsequent HSV-1 infection. In both the RAW264.7 macrophage and PM in vitro models, HSV-1 replication in M1 macrophages was markedly lower than in M2 macrophages and unstimulated controls...
May 10, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28471865/correction-of-cerebrospinal-fluid-protein-in-infants-with-traumatic-lumbar-punctures
#6
Todd W Lyons, Andrea T Cruz, Stephen B Freedman, Joseph L Arms, Paul L Aronson, Alesia H Fleming, Dina M Kulik, Prashant Mahajan, Rakesh D Mistry, Christopher M Pruitt, Amy D Thompson, Lise Nigrovic
In our multi-center cohort of infants ≤ 60 days of age, we identified 2,646 infants with a traumatic lumbar puncture of which 31 (1.2%) had bacterial meningitis. For every 1,000 cerebrospinal fluid (CSF) red blood cells per mm, cerebrospinal (CSF) protein increased 1.1 mg/dL [95% confidence interval (CI) 1.0-1.2 mg/dL].
May 3, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28468883/cxcl10-cxcr3-dependent-mobilization-of-hsv-specific-cd8-tem-and-cd8-trm-cells-within-infected-tissues-allows-efficient-protection-against-recurrent-herpes-infection-and-disease
#7
Ruchi Srivastava, Arif A Khan, Sravya Chilukuri, Sabrina A Syed, Tien T Tran, Julie Furness, Elmostafa Bahraoui, Lbachir BenMohamed
Herpes simplex virus type 1 (HSV-1) establishes latency within the sensory neurons of the trigeminal ganglia (TG). HSV-specific memory CD8(+) T cells play a critical role in preventing HSV-1 reactivation from TG and subsequent virus shedding in tears that trigger recurrent corneal herpetic disease. The CXCL10/CXCR3 chemokine pathway promotes T cell immunity to many viral pathogens, but its importance in CD8(+) T cell immunity to recurrent herpes has been poorly elucidated. In this study, we determined how the CXCL10/CXCR3 pathway affects TG- and cornea-resident CD8(+) T cell responses to recurrent ocular herpes infection and disease using a well-established murine model in which HSV-1 reactivation was induced from latently infected TG by UV-B light...
May 3, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28466551/functionality-testing-of-stem-cell-grafts-to-predict-infectious-complications-after-allogeneic-hematopoietic-stem-cell-transplantation
#8
J Nilsson, I Granrot, J Mattsson, B Omazic, M Uhlin, S Thunberg
BACKGROUND AND OBJECTIVES: Allogeneic hematopoietic stem cell transplantation (HSCT) is a routine clinical procedure performed to treat patients with haematological malignancies, primary immune deficiencies or metabolic disorders. Infections during lymphopenia after allogeneic HSCT are associated with high mortality and morbidity. Typical infectious agents are Epstein-Barr virus, cytomegalovirus, herpes simplex virus, varicella-zoster virus and fungi. The study aim was to evaluate whether measurement of the responses of antigen-specific T-cells, recognizing infectious pathogens would correlate to protective functions in the stem cell recipient post-transplant...
May 2, 2017: Vox Sanguinis
https://www.readbyqxmd.com/read/28462680/does-placental-mdsc-mediated-modulation-of-arginine-levels-help-protect-the-foetus-from-auxotrophic-pathogens
#9
Abdul Qader Tahir Ismail
Myeloid-derived suppressor cells (MDSCs) are immunosuppressive precursors of dendritic cells, macrophages and granulocytes. MDSCs normally quickly differentiate, but have elevated levels in chronic infection and cancer, where they help tumours evade the immune system through induction of T-cell dysfunction. MDSC levels are also raised in pregnancy, and in the neonate. During pregnancy they may help to prevent maternal rejection of the semiallogenic foetus. In the immediate postnatal period they may aid in allowing tolerance of gut microbiological colonisation and non-pathological environmental antigens...
May 2, 2017: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/28439892/cerebrospinal-fluid-cyto-chemokine-profile-during-acute-herpes-simplex-virus-induced-anti-n-methyl-d-aspartate-receptor-encephalitis-and-in-chronic-neurological-sequelae
#10
Kavitha Kothur, Deepak Gill, Melanie Wong, Shekeeb S Mohammad, Sushil Bandodkar, Susan Arbunckle, Louise Wienholt, Russell C Dale
AIM: To examine the cytokine/chemokine profile of cerebrospinal fluid (CSF) during acute herpes simplex virus-induced N-methyl-d-aspartate receptor (NMDAR) autoimmunity and in chronic/relapsing post-herpes simplex virus encephalitis (HSE) neurological syndromes. METHOD: We measured longitudinal serial CSF cyto-/chemokines (n=34) and a glial marker (calcium-binding astroglial protein, S100B) in one patient during acute HSE and subsequent anti-NMDAR encephalitis, and compared the results with those from two patients with anti-NMDAR encephalitis without preceding HSE...
April 25, 2017: Developmental Medicine and Child Neurology
https://www.readbyqxmd.com/read/28409558/in-vitro-detection-of-cholangiocarcinoma-cells-using-a-fluorescent-protein-expressing-oncolytic-herpes-virus
#11
R J S Coelen, M J de Keijzer, R Weijer, V V Loukachov, J K Wiggers, F P J Mul, A C W A van Wijk, Y Fong, M Heger, T M van Gulik
Pathological confirmation is desired prior to high-risk surgery for suspected perihilar cholangiocarcinoma (PHC), but preoperative tissue diagnosis is limited by poor sensitivity of available techniques. This study aimed to validate whether a tumor-specific enhanced green fluorescent protein (eGFP)-expressing oncolytic virus could be used for cholangiocarcinoma (CC) cell detection. Extrahepatic CC cell lines SK-ChA-1, EGI-1, TFK-1 and control cells (primary human liver cells) were exposed to the oncolytic herpes simplex type 1 virus NV1066 for up to 24 h in adherent culture...
May 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28404844/intramuscular-immunization-of-mice-with-the-live-attenuated-herpes-simplex-virus-type-1-hsv-1-vaccine-strain-vc2-expressing-the-equine-herpesvirus-1-ehv-1-glycoprotein-d-gd-generates-anti-ehv-1-immune-responses-in-mice
#12
Shiliang A Liu, Brent A Stanfield, Vladimir N Chouljenko, Shan Naidu, Ingeborg Langohr, Fabio Del Piero, Jacqueline Ferracone, Alma A Roy, Konstantin G Kousoulas
Vaccination remains the best option to combat EHV-1 infection and several different strategies of vaccination have been investigated and developed over the past decades. Herein, we report that the live-attenuated Herpes Simplex Virus Type-1 (HSV-1) VC2 vaccine strain, which has been shown to be unable to enter into neurons and establish latency in mice, can be utilized as a vector for the heterologous expression of the Equine Herpesvirus-1 (EHV-1) glycoprotein D (gD), and that intramuscular immunization of mice resulted in strong anti-viral humoral and cellular immune responses...
April 12, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28378925/evaluation-of-recombinant-adenovirus-vaccines-based-on-glycoprotein-d-and-truncated-ul25-against-herpes-simplex-virus-type-2-in-mice
#13
Wei Liu, Yan Zhou, Ziyan Wang, Zeqiang Zhang, Qizhi Wang, Weiheng Su, Yan Chen, Yan Zhang, Feng Gao, Chunlai Jiang, Wei Kong
The high prevalence of herpes simplex virus 2 (HSV-2) infections in humans necessitates the development of a safe and effective vaccine that will need to induce vigorous T-cell responses to control the viral infection and transmission. We designed rAd-gD2rAd-gD2▵UL25rAd-▵UL25 to investigate whether recombinant replication-defective adenoviruses vaccine could induce specific T cell responses and protect mice against intravaginal HSV-2 challenge compared with FI-HSV-2. The recombinant adenovirus-based HSV-2 showed higher reductions in mortality and stronger antigen-specific T cell responses compared with FI-HSV-2 and the severity of genital lesions in the mice immunized with rAd-gD2▵UL25 was significantly decreased via eliciting IFN-γ-secreting T responses compared with rAd-gD2 and rAd-▵UL25 group in present study...
April 5, 2017: Microbiology and Immunology
https://www.readbyqxmd.com/read/28378806/fibroblast-growth-factor-2-drives-and-maintains-progressive-corneal-neovascularization-following-hsv-1-infection
#14
H R Gurung, M M Carr, K Bryant, A J Chucair-Elliott, D Jj Carr
Herpes simplex virus type 1 (HSV-1) infection of the cornea induces vascular endothelial growth factor A (VEGF-A)-dependent lymphangiogenesis that continues to develop well beyond the resolution of infection. Inflammatory leukocytes infiltrate the cornea and have been implicated to be essential for corneal neovascularization, an important clinically relevant manifestation of stromal keratitis. Here we report that cornea infiltrating leukocytes including neutrophils and T cells do not have a significant role in corneal neovascularization past virus clearance...
April 5, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28378566/immune-response-of-t-cells-during-herpes-simplex-virus-type-1-hsv-1-infection
#15
Jie Zhang, Huan Liu, Bin Wei
Herpes simplex virus type 1 (HSV-1), a neurotropic member of the alphaherpes virus family, is among the most prevalent and successful human pathogens. HSV-1 can cause serious diseases at every stage of life including fatal disseminated disease in newborns, cold sores, eye disease, and fatal encephalitis in adults. HSV-1 infection can trigger rapid immune responses, and efficient inhibition and clearance of HSV-1 infection rely on both the innate and adaptive immune responses of the host. Multiple strategies have been used to restrict host innate immune responses by HSV-1 to facilitate its infection in host cells...
2017: Journal of Zhejiang University. Science. B
https://www.readbyqxmd.com/read/28331843/curative-effect-of-hf10-on-liver-and-peritoneal-metastasis-mediated-by-host-antitumor-immunity
#16
Yoshihiro Hotta, Hideki Kasuya, Itzel Bustos, Yoshinori Naoe, Toru Ichinose, Maki Tanaka, Yasuhiro Kodera
BACKGROUND: HF10 is a highly attenuated type 1 herpes simplex virus (HSV) with proven effective oncolytic effect. Previous investigations have demonstrated that colon cancer mice model treated with HF10 not only had better survival but were also resistant to the reimplantation of the antitumor effect mediated by host antitumor immunity. Importantly, it has also been noted that in mice with antitumors implanted on both sides of the back, an injection of HF10 on only one side strongly restrains not only the injected antitumor but also the non-injected ones...
2017: Oncolytic Virotherapy
https://www.readbyqxmd.com/read/28329211/therapeutic-vaccine-for-genital-herpes-simplex-virus-2-infection-findings-from-a-randomized-trial
#17
David I Bernstein, Anna Wald, Terri Warren, Kenneth Fife, Stephen Tyring, Patricia Lee, Nick Van Wagoner, Amalia Magaret, Jessica B Flechtner, Sybil Tasker, Jason Chan, Amy Morris, Seth Hetherington
Background.: Genital herpes simplex virus type 2 (HSV-2) infection causes recurrent lesions and frequent viral shedding. GEN-003 is a candidate therapeutic vaccine containing HSV-2 gD2∆TMR and ICP4.2, and Matrix-M2 adjuvant. Methods.: Persons with genital herpes were randomized into 3 dose cohorts to receive 3 intramuscular doses 21 days apart of 10 µg, 30 µg, or 100 µg of GEN-003, antigens without adjuvant, or placebo. Participants obtained genital swab specimens twice daily for HSV-2 detection and monitored genital lesions for 28-day periods at baseline and at intervals after the last dose...
March 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28326624/current-status-of-clinical-trials-assessing-oncolytic-virus-therapy-for-urological-cancers
#18
REVIEW
Satoru Taguchi, Hiroshi Fukuhara, Yukio Homma, Tomoki Todo
Oncolytic virus therapy has recently been recognized as a promising new option for cancer treatment. Oncolytic viruses replicate selectively in cancer cells, thus killing them without harming normal cells. Notably, T-VEC (talimogene laherparepvec, formerly called OncoVEX(GM)(-)(CSF) ), an oncolytic herpes simplex virus type 1, was approved by the US Food and Drug Administration for the treatment of inoperable melanoma in October 2015, and was subsequently approved in Europe and Australia in 2016. The efficacies of many types of oncolytic viruses against urological cancers have been investigated in preclinical studies during the past decade, and some have already been tested in clinical trials...
March 21, 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/28326469/hsv-1-interaction-to-3-o-sulfated-heparan-sulfate-in-mouse-derived-drg-explant-and-profiles-of-inflammatory-markers-during-virus-infection
#19
Harsh Sharthiya, Chanmoly Seng, T H Van Kuppevelt, Vaibhav Tiwari, Michele Fornaro
The molecular mechanism of herpes simplex virus (HSV) entry and the associated inflammatory response in the nervous system remain poorly understood. Using mouse-derived ex vivo dorsal root ganglia (DRG) explant model and single cell neurons (SCNs), in this study, we provided a visual evidence for the expression of heparan sulfate (HS) and 3-O-sulfated heparan sulfate (3-OS HS) followed by their interactions with HSV-1 glycoprotein B (gB) and glycoprotein D (gD) during cell entry. Upon heparanase treatment of DRG-derived SCN, a significant inhibition of HSV-1 entry was observed suggesting the involvement of HS role during viral entry...
March 21, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28319448/rationale-and-design-of-a-phase-1-clinical-trial-to-evaluate-hsv-g207-alone-or-with-a-single-radiation-dose-in-children-with-progressive-or-recurrent-malignant-supratentorial-brain-tumors
#20
Alicia M Waters, James M Johnston, Alyssa T Reddy, John Fiveash, Avi Madan-Swain, Kara Kachurak, Asim K Bag, G Yancey Gillespie, James M Markert, Gregory K Friedman
Primary central nervous system tumors are the most common solid neoplasm of childhood and the leading cause of cancer-related death in pediatric patients. Survival rates for children with malignant supratentorial brain tumors are poor despite aggressive treatment with combinations of surgery, radiation, and chemotherapy, and survivors often suffer from damaging lifelong sequelae from current therapies. Novel innovative treatments are greatly needed. One promising new approach is the use of a genetically engineered, conditionally replicating herpes simplex virus (HSV) that has shown tumor-specific tropism and potential efficacy in the treatment of malignant brain tumors...
March 2017: Human Gene Therapy. Clinical Development
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