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https://www.readbyqxmd.com/read/29237844/hsv-1-dna-polymerase-rnase-h-activity-acts-in-a-3-5-direction-and-is-dependent-on-the-3-5-exonuclease-active-site
#1
Jessica L Lawler, Purba Mukherjee, Donald M Coen
The catalytic subunit (Pol) of herpes simplex virus-1 (HSV-1) DNA polymerase has been extensively studied both as a model for other family B DNA polymerases and for its differences from these enzymes as an antiviral target. Among the activities of HSV-1 Pol is an intrinsic RNase H activity that cleaves RNA from RNA:DNA hybrids. There has long been a controversy regarding whether this activity is due to the 3' -5' exonuclease of Pol or whether it is a separate activity, possibly acting on 5' RNA termini. To investigate this issue, we compared wild-type HSV-1 Pol and a 3' -5' exonuclease-deficient mutant, D368A, for DNA polymerase activity, 3' -5' exonuclease activity, and RNase H activity in vitro Additionally, we assessed the RNase H activity using differentially end-labeled templates with 5' or 3' RNA termini...
December 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29228551/human-cytomegalovirus-and-herpes-simplex-type-i-virus-can-engage-rna-polymerase-i-for-transcription-of-immediate-early-genes
#2
Ourania N Kostopoulou, Vanessa Wilhelmi, Sina Raiss, Sharan Ananthaseshan, Mikael S Lindström, Jiri Bartek, Cecilia Söderberg-Naucler
Human cytomegalovirus (HCMV) utilizes RNA polymerase II to transcribe viral genes and produce viral mRNAs. It can specifically target the nucleolus to facilitate viral transcription and translation. As RNA polymerase I (Pol I)-mediated transcription is active in the nucleolus, we investigated the role of Pol I, along with relative contributions of the human Pol II and Pol III, to early phases of viral transcription in HCMV infected cells, compared with Herpes Simplex Virus-1 (HSV-1) and Murine cytomegalovirus (MCMV)...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29224963/meeting-report-initial-world-health-organization-consultation-on-herpes-simplex-virus-hsv-vaccine-preferred-product-characteristics-march-2017
#3
Sami L Gottlieb, Birgitte K Giersing, Julian Hickling, Rebecca Jones, Carolyn Deal, David C Kaslow
The development of vaccines against herpes simplex virus (HSV) is an important global goal for sexual and reproductive health. A key priority to advance development of HSV vaccines is the definition of preferred product characteristics (PPCs), which provide strategic guidance on World Health Organization (WHO) preferences for new vaccines, specifically from a low- and middle-income country (LMIC) perspective. To start the PPC process for HSV vaccines, the WHO convened a global stakeholder consultation in March 2017, to define the priority public health needs that should be addressed by HSV vaccines and discuss the key considerations for HSV vaccine PPCs, particularly for LMICs...
December 7, 2017: Vaccine
https://www.readbyqxmd.com/read/29219053/triazolopyrimidines-and-thiazolopyrimidines-synthesis-anti-hsv-1-cytotoxicity-and-mechanism-of-action
#4
Salwa F Mohamed, Eman M H Abbas, Hemat S Khalaf, Thoraya A Farghaly, Dina N Abd El-Shafy
Merged pyrimidine derivatives were designed by one pot synthesis of pyrimidinethione derivative with halogenated compounds. The structure of all prepared compounds was characterized by their spectroscopic data and also, their ability to inhibit the in vitro replication of HSV-1 was estimated. Amongst the tested compounds 2-acetyl-3-methyl-5-(p-tolyl)indeno[1,2-d]thiazolo[3,2-a]pyrimidin-6(5H)-one (9b) and ethyl 3-methyl-6-oxo-5-(p-tolyl)-5,6-dihydroindeno[1,2-d]thiazolo[3,2-a]pyrimidine-2-carboxylate (9c), caused viral inhibition over 90%...
December 7, 2017: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/29216761/efficient-therapeutic-protein-expression-using-retroviral-replicating-vector-with-2a-peptide-in-cancer-models
#5
Andrew Hofacre, Kader Yagiz, Daniel Mendoza, Fernando Lopez Espinoza, Anthony Munday, Cindy Burrascano, Oded Singer, Harry Gruber, Doug Jolly, Amy Lin
Toca 511, a retroviral replicating vector (RRV), uses an internal ribosomal entry site (IRES) to express an optimized yeast cytosine deaminase (yCD2), which converts 5-fluorocytosine to 5-fluorouracil. This configuration is genetically stable in both preclinical mouse models and human clinical trials. However, the use of IRES (~ 600 bp) restricts choices of therapeutic transgenes due to limits in RRV genome size. In this study, we replaced IRES with 2A peptides derived from picornaviruses with or without a GSG linker...
December 7, 2017: Human Gene Therapy
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
#6
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/29216362/an-hsv-2-single-cycle-candidate-vaccine-deleted-in-glycoprotein-d-%C3%AE-gd-2-protects-male-mice-from-lethal-skin-challenge-with-clinical-isolates-of-hsv-1-and-hsv-2
#7
Clare Burn, Natalie Ramsey, Scott J Garforth, Steven Almo, William R Jacobs, Betsy C Herold
HSV infections manifest as recurrent oral or genital mucosal lesions, meningoencephalitis, corneal blindness and perinatal disease. Subunit vaccines have advanced into the clinic without success. None were tested preclinically in male mice. We compared a single-cycle candidate vaccine deleted in HSV-2 glycoprotein D (ΔgD-2) and subunit gD-2 or gD-1 protein vaccines in a male murine skin model. ΔgD-2 provided complete protection against 10-times the lethal dose of HSV-1 or HSV-2 clinical isolates and no latent virus was detected, whereas gD-1 and gD-2 adjuvanted proteins provided little or no protection...
December 5, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29216315/the-pul37-tegument-protein-guides-alpha-herpesvirus-retrograde-axonal-transport-to-promote-neuroinvasion
#8
Alexsia L Richards, Patricia J Sollars, Jared D Pitts, Austin M Stults, Ekaterina E Heldwein, Gary E Pickard, Gregory A Smith
A hallmark property of the neurotropic alpha-herpesvirinae is the dissemination of infection to sensory and autonomic ganglia of the peripheral nervous system following an initial exposure at mucosal surfaces. The peripheral ganglia serve as the latent virus reservoir and the source of recurrent infections such as cold sores (herpes simplex virus type I) and shingles (varicella zoster virus). However, the means by which these viruses routinely invade the nervous system is not fully understood. We report that an internal virion component, the pUL37 tegument protein, has a surface region that is an essential neuroinvasion effector...
December 7, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29214036/strong-viral-associations-with-sle-among-filipinos
#9
Evan S Vista, Michael H Weisman, Mariko L Ishimori, Hua Chen, Rebecka L Bourn, Ben F Bruner, Laniyati Hamijoyo, Robelle D Tanangunan, Noga J Gal, Julie M Robertson, John B Harley, Joel M Guthridge, Sandra V Navarra, Judith A James
Objectives: Epstein-Barr virus (EBV) is considered an important environmental factor in SLE aetiology, but the relationship between SLE and EBV in the Filipino population is unknown. We tested associations between SLE, lupus-associated autoantibodies and seropositivity for EBV and other herpes viruses in the Filipino population. Methods: Sera from Filipino patients with SLE (n=233), unaffected first-degree relatives (FDRs, n=543) and unrelated controls (n=221) were tested for antibodies against EBV, cytomegalovirus (CMV) and herpes simplex viruses (HSV-1 and HSV-2) by standardised ELISAs...
2017: Lupus Science & Medicine
https://www.readbyqxmd.com/read/29207707/diagnostic-approach-to-viral-acute-encephalitis-syndrome-aes-in-paediatric-age-group-a-study-from-new-delhi
#10
Shipra Goel, Anita Chakravarti, Mukta Mantan, Surinder Kumar, Md Anzar Ashraf
Introduction: Acute Encephalitis Syndrome has heralded the emergence of multiple virulent pathogens, which may result in severe morbidity and mortality. In India, encephalitis is not notified and there has been a dearth of analysis for trends in encephalitis death rates and causation. A downward trend has been observed in encephalitis deaths, due to 'known' causes, which can be largely explained by improvement in diagnostic, treatment, and prevention methods. There is still a very high proportion of encephalitis deaths in developing countries, where the aetiological diagnosis of the pathogen is not established and thus, lies the importance of monitoring encephalitis morbidity and mortality with a view to improve pathogen diagnosis and identify emerging infectious diseases...
September 2017: Journal of Clinical and Diagnostic Research: JCDR
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
#11
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/29198810/short-duration-ocular-iontophoresis-of-ionizable-aciclovir-prodrugs-a-new-approach-to-treat-herpes-simplex-infections-in-the-anterior-and-posterior-segments-of-the-eye
#12
Yong Chen, Yogeshvar N Kalia
The objective was to investigate (trans)corneal and transscleral iontophoresis of biolabile amino acid ester prodrugs of aciclovir (ACV-X, X = Arg, Gly and Trp) as a means to increase ocular bioavailability of ACV. Prodrugs displayed tissue-dependent susceptibility to hydrolysis. Iontophoresis of ACV-Arg, ACV-Gly and ACV-Trp (5 mM, 0.5 mA/cm2) for 5 min followed by 55 min passive diffusion resulted in appreciable corneal deposition (21.5 ± 5.1, 14.1 ± 2.0 and 5.3 ± 0.6 nmol/cm2, respectively) and transcorneal permeation (13...
November 30, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29198180/converging-epidemics-of-sexually-transmitted-infections-and-bacterial-vaginosis-in-southern-african-female-adolescents-at-risk-of-hiv
#13
Shaun L Barnabas, Smritee Dabee, Jo-Ann S Passmore, Heather B Jaspan, David A Lewis, Shameem Z Jaumdally, Hoyam Gamieldien, Lindi Masson, Etienne Muller, Venessa D Maseko, Nonhlanhla Mkhize, Zizipho Mbulawa, Anna-Lise Williamson, Clive M Gray, Thomas J Hope, Francesca Chiodi, Janan Dietrich, Glenda Gray, Linda-Gail Bekker
Adolescents in Africa are at high risk for HIV infection, other sexually transmitted infections (STIs) and bacterial vaginosis (BV). Since behavior and burden of STIs/BV may influence HIV risk, behavioral risk factors and prevalence of STIs/BV were compared in HIV-seronegative adolescent females (n = 298; 16-22 years) from two South African communities (Soweto and Cape Town). STIs ( Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Mycoplasma genitalium, herpes simplex virus (HSV)-1, HSV-2, Treponema pallidum, and Haemophilus ducreyi) were detected by multiplex polymerase chain reaction, human papillomavirus (HPV) by Roche Linear Array, and BV by Nugent scoring...
January 1, 2017: International Journal of STD & AIDS
https://www.readbyqxmd.com/read/29197712/radiotherapy-induced-reactivation-of-neurotrophic-human-herpes-viruses-overview-and-management
#14
REVIEW
Marigdalia K Ramirez-Fort, Jianying Zeng, Amir Feily, Luis A Ramirez-Pacheco, Joseph M Jenrette, David L Mayhew, Talal Syed, S Lewis Cooper, Craig Linden, Witney S Graybill, Lars E French, Christopher S Lange
PURPOSE: Infection by Human Herpes Viruses (HHV) types 1-3, are prevalent throughout the world. It is known that radiotherapy can reactivate HHVs, but it is unclear how and to what extent reactivations can interact with or affect radiotherapeutic efficacy, patient outcomes and mortality risk. Herein, we aim to summarize what is known about Herpes Simplex Virus (HSV)-1,2 and Varicella Zoster Virus (VZV) pathophysiology as it relates to tumor biology, radiotherapy, chemo-radiotherapy, diagnosis and management so as to optimize cancer treatment in the setting of active HHV infection...
November 22, 2017: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/29189153/antiviral-effects-of-saffron-and-its-major-ingredients
#15
Sepehr Soleymani, Rezvan Zabihollahi, Sepideh Shahbazi, Azam Bolhassani
The lack of an effective vaccine against viral infections, toxicity of the synthetic anti-viral drugs and the generation of resistant viral strains led to discover novel inhibitors. Recently, saffron and its compounds were used to treat different pathological conditions. In this study, we tested the anti-HSV-1 and anti-HIV-1 activities of Iranian saffron extract and its major ingredients including crocin and picrocrocin as well as cytotoxicity in vitro. The data showed that the aqueous saffron extract was not active against HIV-1 and HSV-1 virions at certain doses (i...
November 29, 2017: Current Drug Delivery
https://www.readbyqxmd.com/read/29188714/secoheliosphanes-a-and-b-and-secoheliospholane-a-three-diterpenoids-with-unusual-seco-jatrophane-and-seco-jatropholane-skeletons-from-euphorbia-helioscopia
#16
Zhen-Peng Mai, Gang Ni, Yan-Fei Liu, Yu-Huan Li, Li Li, Jia-Yuan Li, De-Quan Yu
Secoheliosphanes A (1) and B (2) and secoheliospholane A (3), possessing an unusual 7,8-seco-jatrophane skeleton and an unprecedented 9,10-seco-7,10-epoxyjatropholane skeleton, respectively, were isolated from the whole plants of Euphorbia helioscopia, along with two biogenetically precursors, a new jatrophane diterpene, 2-epi-euphornin I (4) and a known jatrophane diterpene, euphoscopin A (5). Structures of 1-4 including absolute configurations were elucidated on the basis of spectroscopic data, X-ray crystallography, and chemical conversion...
November 30, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/29187538/the-absence-of-dhhc3-affects-primary-and-latent-hsv-1-infection
#17
Shaohui Wang, Kevin R Mott, Marianne Cilluffo, Casey L Kilpatrick, Shoko Murakami, Alexander V Ljubimov, Konstantin G Kousoulas, Sita Awasthi, Bernhard Luscher, Homayon Ghiasi
UL20, an essential HSV-1 protein, is involved in cytoplasmic envelopment of virions and virus egress. We reported recently that UL20 can bind to a host protein encoded by the zinc finger DHHC-type containing 3 (ZDHHC3) gene (also known as Golgi-specific DHHC zinc finger protein {GODZ}). Here, we show for the first time that HSV-1 replication is compromised in murine embryonic fibroblasts (MEFs) isolated from GODZ-/- mice. The absence of GODZ resulted in reduced palmitoylation of UL20 and altered localization, expression of UL20 and gK; the expression of gB and gC; and the localization and expression of tegument and capsid proteins within HSV-1-infected MEFs...
November 29, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29186456/the-anti-hiv-drug-tenofovir-a-reverse-transcriptase-inhibitor-also-targets-the-herpes-simplex-virus-hsv-dna-polymerase
#18
Graciela Andrei, Sarah Gillemot, Dimitrios Topalis, Robert Snoeck
Background: Genital herpes is an important cofactor for acquisition of HIV infection and effective prophylaxis is a helpful strategy to halt both HIV and HSV transmission. The antiretroviral agent tenofovir, formulated as a vaginal microbicide gel, was shown to reduce the risk of HIV and HSV-2 acquisition. Methods: HSV-1 and HSV-2 mutants were selected for resistance to tenofovir and PMEO-DAPy (an acyclic nucleoside phosphonate with dual anti-HSV and anti-HIV activity) by stepwise dose escalation...
November 23, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29186188/effect-of-age-on-chronic-inflammation-and-responsiveness-to-bacterial-and-viral-challenges
#19
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/29185708/the-autophagy-related-beclin-1-protein-requires-both-the-coiled-coil-and-bara-domains-to-form-a-homodimer-with-sub-micromolar-affinity
#20
Matthew J Ranaghan, Michael A Durney, Michael F Mesleh, Patrick R McCarren, Colin W Garvie, Douglas S Daniels, Kimberly L Carey, Adam P Skepner, Beth Levine, José Perez
Beclin-1 (BECN1) is an essential component of macroautophagy. This process is a highly-conserved survival mechanism that recycles damaged cellular components or pathogens by encasing them in a bilayer vesicle that fuses with a lysosome to enable degradation of the vesicular contents. Mutations or altered expression profiles of BECN1 have been linked to various cancers and neurodegenerative diseases. Viruses, including HIV and Herpes Simplex Virus 1 (HSV-1), are also known to specifically target BECN1 as a means to evade host defense mechanisms...
November 29, 2017: Biochemistry
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