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JOURNAL ARTICLE
Hong-Xing Pan, Ling-Xian Qiu, Qi Liang, Zhen Chen, Ming-Lei Zhang, Sheng Liu, Guo-Hua Zhong, Kong-Xin Zhu, Meng-Jun Liao, Jia-Lei Hu, Jia-Xue Li, Jin-Bo Xu, Yong Fan, Yue Huang, Ying-Ying Su, Shou-Jie Huang, Wei Wang, Jin-Le Han, Ji-Zong Jia, Hua Zhu, Tong Cheng, Xiang-Zhong Ye, Chang-Gui Li, Ting Wu, Feng-Cai Zhu, Jun Zhang, Ning-Shao Xia
BACKGROUND: The Oka varicella vaccine strain remains neurovirulent and can establish lifelong latent infection, raising safety concerns about vaccine-related herpes zoster. In this study, we aimed to evaluate the immunogenicity and safety of a skin-attenuated and neuro-attenuated varicella vaccine candidate (v7D vaccine). METHODS: We did this randomised, double-blind, controlled, phase 2a clinical trial in Jiangsu, China. Healthy children aged 3-12 years with no history of varicella infection or vaccination were enrolled and randomly assigned (1:1:1:1) to receive a single subcutaneous injection of the v7D vaccine at 3·3 log10 plaque forming units (PFU; low-dose v7D group), 3·9 log10 PFU (medium-dose v7D group), and 4·2 log10 PFU (high-dose v7D group), or the positive control varicella vaccine (vOka vaccine group)...
April 10, 2024: Lancet Infectious Diseases
#2
JOURNAL ARTICLE
Ahmad S Rashidi, Diana N Tran, Caithlin R Peelen, Michiel van Gent, Werner J D Ouwendijk, Georges M G M Verjans
BACKGROUND: Herpes simplex virus (HSV) encephalitis (HSE) is a serious and potentially life-threatening disease, affecting both adults and newborns. Progress in understanding the virus and host factors involved in neonatal HSE has been hampered by the limitations of current brain models that do not fully recapitulate the tissue structure and cell composition of the developing human brain in health and disease. Here, we developed a human fetal organotypic brain slice culture (hfOBSC) model and determined its value in mimicking the HSE neuropathology in vitro...
February 1, 2024: Journal of Neuroinflammation
#3
JOURNAL ARTICLE
Alexander L Ling, Isaac H Solomon, Ana Montalvo Landivar, Hiroshi Nakashima, Jared K Woods, Andres Santos, Nafisa Masud, Geoffrey Fell, Xiaokui Mo, Ayse S Yilmaz, James Grant, Abigail Zhang, Joshua D Bernstock, Erickson Torio, Hirotaka Ito, Junfeng Liu, Naoyuki Shono, Michal O Nowicki, Daniel Triggs, Patrick Halloran, Raziye Piranlioglu, Himanshu Soni, Brittany Stopa, Wenya Linda Bi, Pierpaolo Peruzzi, Ethan Chen, Seth W Malinowski, Michael C Prabhu, Yu Zeng, Anne Carlisle, Scott J Rodig, Patrick Y Wen, Eudocia Quant Lee, Lakshmi Nayak, Ugonma Chukwueke, L Nicolas Gonzalez Castro, Sydney D Dumont, Tracy Batchelor, Kara Kittelberger, Ekaterina Tikhonova, Natalia Miheecheva, Dmitry Tabakov, Nara Shin, Alisa Gorbacheva, Artemy Shumskiy, Felix Frenkel, Estuardo Aguilar-Cordova, Laura K Aguilar, David Krisky, James Wechuck, Andrea Manzanera, Chris Matheny, Paul P Tak, Francesca Barone, Daniel Kovarsky, Itay Tirosh, Mario L Suvà, Kai W Wucherpfennig, Keith Ligon, David A Reardon, E Antonio Chiocca
Immunotherapy failures can result from the highly suppressive tumour microenvironment that characterizes aggressive forms of cancer such as recurrent glioblastoma (rGBM)1,2 . Here we report the results of a first-in-human phase I trial in 41 patients with rGBM who were injected with CAN-3110-an oncolytic herpes virus (oHSV)3 . In contrast to other clinical oHSVs, CAN-3110 retains the viral neurovirulence ICP34.5 gene transcribed by a nestin promoter; nestin is overexpressed in GBM and other invasive tumours, but not in the adult brain or healthy differentiated tissue4 ...
October 18, 2023: Nature
#4
JOURNAL ARTICLE
Karol Perlejewski, Marek Radkowski, Agnieszka Pawełczyk, Małgorzata Rydzanicz, Tomasz Dzieciątkowski, Michał Makowiecki, Marcin Paciorek, Renata Welc-Falęciak, Andrzej Horban, Tomasz Laskus
Patients with Lyme neuroborreliosis (LNB) are rarely tested for the presence of neurovirulent viruses other than tick-borne encephalitis virus (TBEV); however, such coinfections could be of clinical importance. The aim of the study was to search for the presence of neurotropic viruses in a LNB patients. Fourteen patients admitted with signs and symptoms of neuroinfection who were eventually diagnosed to have LNB (according to the guidelines of the European Federation of Neurological Societies) were subjects of the study...
September 18, 2023: Ticks and Tick-borne Diseases
#5
JOURNAL ARTICLE
Aaron W Kolb, Sarah A Ferguson, Inna V Larsen, Curtis R Brandt
Sex related differences in the incidence or severity of infection have been described for multiple viruses. With herpes simplex viruses, the best example is HSV-2 genital infection where women have a higher incidence of infection and can have more severe infections than men. HSV-1 causes several types of infections including skin and mucosal ulcers, keratitis, and encephalitis in humans that do not appear to have a strong biological sex component. Given that mouse strains differ in their MHC loci it is important to determine if sex differences occur in multiple strains of mice...
2023: PloS One
#6
JOURNAL ARTICLE
Cooper K Hayes, Christopher K Villota, Fiona B McEnany, Stacey Cerón, Sita Awasthi, Moriah L Szpara, Harvey M Friedman, David A Leib, Richard Longnecker, Matthew D Weitzman, Lisa N Akhtar
Herpes simplex virus (HSV) infection of the neonatal brain causes severe encephalitis and permanent neurologic deficits. However, infants infected with HSV at the time of birth follow varied clinical courses, with approximately half of infants experiencing only external infection of the skin rather than invasive neurologic disease. Understanding the cause of these divergent outcomes is essential to developing neuroprotective strategies. To directly assess the contribution of viral variation to neurovirulence, independent of human host factors, we evaluated clinical HSV isolates from neonates with different neurologic outcomes in neurologically-relevant in vitro and in vivo models...
April 22, 2022: Journal of Infectious Diseases
#7
REVIEW
Meishen Ren, Yin Wang, Yan Luo, Xueping Yao, Zexiao Yang, Pengfei Zhang, Wei Zhao, Dike Jiang
Neurotropic viruses have neural-invasive and neurovirulent properties to damage the central nervous system (CNS), leading to humans' fatal symptoms. Neurotropic viruses comprise a lot of viruses, such as Zika virus (ZIKV), herpes simplex virus (HSV), rabies virus (RABV), and severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). Effective therapy is needed to prevent infection by these viruses in vivo and in vitro . However, the blood-brain barrier (BBB) usually prevents macromolecules from entering the CNS, which challenges the usage of the traditional probes, antiviral drugs, or neutralizing antibodies in the CNS...
2021: Frontiers in Microbiology
#8
JOURNAL ARTICLE
Alberto Domingo López-Muñoz, Alberto Rastrojo, Kai A Kropp, Abel Viejo-Borbolla, Antonio Alcamí
Herpes simplex virus serotype 2 (HSV-2) is a ubiquitous human pathogen that causes recurrent genital infections and ulcerations. Many HSV-2 strains with different biological properties have been identified, but only the genomes of HSV-2 strains HG52, SD90e and 333 have been reported as complete and fully characterized sequences. We de novo assembled, annotated and manually curated the complete genome sequence of HSV-2 strain MS, a highly neurovirulent strain, originally isolated from a multiple sclerosis patient...
June 2021: Microbial Genomics
#9
JOURNAL ARTICLE
Lei Liu, Jishuai Cheng, Tangwei Mou, Ying Zhang, Xingli Xu, Jingjing Zhang, Xueqi Li, Xiao Feng, Xiangxiong Xu, Yun Liao, Shengtao Fan, Lichun Wang, Guorun Jiang, Qihan Li
HSV-2 (Herpes simplex virus type 2) is a critical viral agent that mainly causes genital herpes and life-long latent infection in the dorsal root ganglia. Gene modification via CRISPR/Cas9 Clustered regularly interspaced short palindromic repeat sequences/CRISPR associated 9) was used here to construct HSV-2 mutant strains through the deletion of fragments of the RL1 (Repeat Long element 1) and/or LAT (Latency-associated Transcript) genes. The HSV-2 mutant strains LAT- HSV-2 and RL1-LAT- HSV-2 present different biological properties...
July 17, 2020: Viruses
#10
JOURNAL ARTICLE
E Antonio Chiocca, Hiroshi Nakashima, Kazue Kasai, Soledad A Fernandez, Michael Oglesbee
rQNestin34.5v.2 is an oncolytic herpes simplex virus 1 (oHSV) that retains expression of the neurovirulent ICP34.5 gene under glioma-selective transcriptional regulation. To prepare an investigational new drug (IND) application, we performed toxicology and efficacy studies of rQNestin34.5v.2 in mice in the presence or absence of the immunomodulating drug cyclophosphamide (CPA). ICP34.5 allows HSV1 to survive interferon and improves viral replication by dephosphorylation of the eIF-2α translation factor. rQNestin34...
June 12, 2020: Molecular Therapy. Methods & Clinical Development
#11
JOURNAL ARTICLE
Charles Grose, Lynn W Enquist
The neurovirulence of the live attenuated varicella vaccine virus is a subject of increasing interest. Since there is no ideal animal model for varicella-zoster virus (VZV) infection and neuropathogenesis, we have turned to animal models for the closely related pseudorabies virus (PRV). PRV is the alpha herpes virus of swine; the first live attenuated PRV vaccine (Bartha strain) was produced in 1961 in Hungary, a decade before the live attenuated VZV vaccine (Oka strain) was produced in Japan. Neurologic disease caused by PRV often resembles neurologic disease caused by VZV...
January 13, 2020: Journal of Medical Virology
#12
JOURNAL ARTICLE
Katrien C K Poelaert, Jolien Van Cleemput, Kathlyn Laval, Jiexiong Xie, Herman W Favoreel, Hans J Nauwynck
The ancestral equine herpesvirus 1 (EHV1), closely related to human herpes viruses, exploits leukocytes to reach its target organs, accordingly evading the immune surveillance system. Circulating EHV1 strains can be divided into abortigenic/neurovirulent, causing reproductive/neurological disorders. Neurovirulent EHV1 more efficiently recruits monocytic CD172a+ cells to the upper respiratory tract (URT), while abortigenic EHV1 tempers monocyte migration. Whether similar results could be expected for T lymphocytes is not known...
September 6, 2019: Journal of General Virology
#13
JOURNAL ARTICLE
Lisa N Akhtar, Christopher D Bowen, Daniel W Renner, Utsav Pandey, Ashley N Della Fera, David W Kimberlin, Mark N Prichard, Richard J Whitley, Matthew D Weitzman, Moriah L Szpara
More than 14,000 neonates are infected with herpes simplex virus (HSV) annually. Approximately half display manifestations limited to the skin, eyes, or mouth (SEM disease). The rest develop invasive infections that spread to the central nervous system (CNS disease or encephalitis) or throughout the infected neonate (disseminated disease). Invasive HSV disease is associated with significant morbidity and mortality, but the viral and host factors that predispose neonates to these forms are unknown. To define viral diversity within the infected neonatal population, we evaluated 10 HSV-2 isolates from newborns with a range of clinical presentations...
February 27, 2019: MSphere
#14
JOURNAL ARTICLE
Audra J Charron, Stephen L Ward, Brian J North, Stacey Ceron, David A Leib
Herpes simplex virus type 1 (HSV-1) cycles between phases of latency in sensory neurons and replication in mucosal sites. HSV-1 encodes two key proteins that antagonize the shutdown of host translation; US11 through preventing PKR activation, and ICP34.5 through mediating eIF2α dephosphorylation. While the profound attenuation of ICP34.5 deletion mutants has been repeatedly demonstrated, a role for US11 in HSV-1 pathogenesis remains unclear. We therefore generated an HSV-1 strain 17 US11 null virus and examined its properties in vitro and in vivo In U373 glioblastoma cells, US11 cooperated with ICP34...
February 13, 2019: Journal of Virology
#15
JOURNAL ARTICLE
Lin Cheng, Hua Jiang, Jingjing Fan, Jiani Wang, Pan Hu, Ying Ruan, Renbin Liu
Oncolytic herpes simplex virus-1 (oHSV-1) vectors are promising therapeutic agents for cancer. The deletion of the γ34.5 gene eliminates the neurovirulence but attenuates virus replication at the same time. The carboxyl-terminus of protein phosphatase 1 regulatory subunit 15A (also known as MyD116/GADD34) is homologous to that of γ34.5; hence, it may substitute for γ34.5 to enhance the replication and cytotoxicity of the virus. To investigate whether the C-terminus of MyD116 can enhance the anti-tumour efficacy of G47Δ on human breast cancer cells, a GD116 mutant was constructed by inserting a γ34...
May 2018: Oncology Letters
#16
JOURNAL ARTICLE
Y Furukawa, A Takasu, Y Yura
Herpes simplex virus type 1 (HSV-1) is one of the most widely studied viruses for oncolytic virotherapy. In squamous cell carcinoma (SCC) cells, the role of autophagy induced by neurovirulence gene-deficient HSV-1s in programmed cell death has not yet been elucidated. The oncolytic HSV-1 strain RH2, which lacks the γ34.5 gene and induces the fusion of human SCC cells, was used. RH2 replicated and induced cell death in SCC cells. RH2 infection was accompanied by the aggregation of microtubule-associated protein 1 light chain 3 (LC3) in the cytoplasm, the conversion of LC3-I to LC3-II and the formation of double-membrane vacuoles containing cell contents...
September 2017: Cancer Gene Therapy
#17
JOURNAL ARTICLE
Richard Manivanh, Jesse Mehrbach, David M Knipe, David A Leib
During viral infection, pattern recognition receptors (PRRs) and their associated adaptors recruit TANK-binding kinase 1 (TBK1) to activate interferon regulatory factor 3 (IRF3), resulting in production of type I interferons (IFNs). ICP0 and ICP34.5 are among the proteins encoded by herpes simplex virus 1 (HSV-1) that modulate type I IFN signaling. We constructed a recombinant virus (ΔXX) that lacks amino acids 87 to 106, a portion of the previously described TBK1-binding domain of the γ34.5 gene (D. Verpooten, Y...
December 1, 2017: Journal of Virology
#18
JOURNAL ARTICLE
Valerio Leoni, Valentina Gatta, Costanza Casiraghi, Alfredo Nicosia, Biljana Petrovic, Gabriella Campadelli-Fiume
The oncolytic herpes simplex virus (HSV) that has been approved for clinical practice and those HSVs in clinical trials are attenuated viruses, often with the neurovirulence gene γ1 34.5 and additional genes deleted. One strategy to engineer nonattenuated oncolytic HSVs consists of retargeting the viral tropism to a cancer-specific receptor of choice, exemplified by HER2 (human epidermal growth factor receptor 2), which is present in breast, ovary, and other cancers, and in detargeting from the natural receptors...
May 15, 2017: Journal of Virology
#19
LETTER
Outi Heikkilä, Elina Ryödi, Veijo Hukkanen
No abstract text is available yet for this article.
December 1, 2016: Journal of Virology
#20
JOURNAL ARTICLE
Xingli Xu, Shengtao Fan, Jienan Zhou, Ying Zhang, Yanchun Che, Hongzhi Cai, Lichun Wang, Lei Guo, Longding Liu, Qihan Li
BACKGROUND: UL7, a tegument protein of Herpes Simplex Virus type I (HSV-1), is highly conserved in viral infection and proliferation and has an unknown mechanism of action. METHODS: A HSV-1 UL7 mutant (UL7-MU) was constructed using the CRISPR-cas9 system. The replication rate and plaque morphology were used to analyze the biological characteristics of the wild-type (WT), UL7-MU and MU-complemented P1 viruses. The virulence of the viruses was evaluated in mice. Real-time RT-qPCR and ChIP assays were used to determine the expression levels of relevant genes...
September 13, 2016: Virology Journal
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