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https://www.readbyqxmd.com/read/29161560/immunity-insect-immune-memory-goes-viral
#1
Petros Ligoxygakis
Adaptive memory in insect immunity has been controversial. In this issue, Andino and co-workers propose that acquisition of viral sequences in the host genome gives rise to anti-sense, anti-viral piRNAs. Such sequences can be regarded as both a genomic archive of past infections and as an armour of potential heritable memory.
November 20, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/29161301/detection-and-quantification-of-dengue-virus-using-a-novel-biosensor-system-based-on-dengue-ns3-protease-activity
#2
Ming-Shu Hsieh, Mei-Yu Chen, Chun-Hsiang Hsieh, Chien-Hsiung Pan, Guann-Yi Yu, Hsin-Wei Chen
BACKGROUND: The traditional methods, plaque assays and immuno-focus assays, used to titrate infectious dengue virus (DENV) particles are time consuming and labor intensive. Here, we developed a DENV protease activity detection system (DENPADS) to visualize DENV infection in cells based on dengue protease activity. METHODOLOGY/PRINCIPAL FINDINGS: Dengue NS3 protease cleaves NS4B-NS5. BHK-21 cells stably expressing the sensor module comprising DENV-2 NS4 and the 10 amino-terminal amino acids of NS5 (N10NS5) fused with the SV40 nuclear localization signal (NLS) and Cre recombinase (Cre), were generated...
2017: PloS One
https://www.readbyqxmd.com/read/29159280/insertion-of-the-type-i-ifn-decoy-receptor-b18r-in-a-mirna-tagged-semliki-forest-virus-improves-oncolytic-capacity-but-results-in-neurotoxicity
#3
Tina Sarén, Mohanraj Ramachandran, Miika Martikainen, Di Yu
Oncolytic Semliki Forest virus (SFV) has been suggested as a potential candidate for the treatment of glioblastoma and neuroblastoma. However, the oncolytic capacity of SFV is restricted by the anti-viral type-I interferon (IFN) response. The aim of this study was to increase the oncolytic capacity of a microRNA target tagged SFV against glioblastoma by arming it with the Vaccinia-virus-encoded type-I IFN decoy receptor B18R (SFV4B18RmiRT) to neutralize type-I IFN response. Expression of B18R by SFV4B18RmiRT aided neutralization of IFN-β, which was shown by reduced STAT-1 phosphorylation and improved virus spread in plaque assays...
December 15, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/29159022/chinese-herbal-medicine-compound-yi-zhi-hao-pellet-inhibits-replication-of-influenza-virus-infection-through-activation-of-heme-oxygenase-1
#4
Jinqiu Yin, Linlin Ma, Huiqiang Wang, Haiyan Yan, Jin Hu, Wen Jiang, Yuhuan Li
As a leading cause of respiratory disease, influenza A virus (IAV) presents a pandemic threat in annual seasonal outbreaks. Given the limitation of existing anti-influenza therapies, there remains to be a requirement for new drugs. Compound Yi-Zhi-Hao pellet (CYZH) is a famous traditional Chinese medicine (TCM) used in the clinic, whose formula has been recorded in Complication of National Standard for Traditional Chinese Medicine to treat common cold. In this study, we found that CYZH exhibited a broad-spectrum anti-influenza activity and inhibited the expression of viral RNA and proteins in vitro...
November 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/29157813/anti-inflammatory-and-antiviral-activities-of-cynanversicoside-a-and-cynanversicoside-c-isolated-from-cynanchun-paniculatum-in-influenza-a-virus-infected-mice-pulmonary-microvascular-endothelial-cells
#5
Panying Wei, Tao Zhang, Hong Dong, Qiaohong Chen, Xiang Mu, Ge Hu
BACKGROUND: Outbreaks of the influenza A virus (IAV) often occur in various avian and mammalian species, including humans, causing serious respiratory injury worldwide. Therapeutic actions are limited to vaccines and a few antiviral drugs. Combination antiviral compounds and anti-inflammatory modulators to control the propagation of viruses would be more efficient therapeutic strategies for infectious diseases. PURPOSE: This study was designed to isolate anti-inflammatory and antiviral compounds from Cynanchun paniculatum and elucidate their potential molecular mechanisms...
December 1, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29156834/oncolytic-reovirus-inhibits-angiogenesis-through-induction-of-cxcl10-ip-10-and-abrogation-of-hif-activity-in-soft-tissue-sarcomas
#6
Jennifer S Carew, Claudia M Espitia, Weiguo Zhao, Monica M Mita, Alain C Mita, Steffan T Nawrocki
The tumor-selective viral replication capacity and pro-apoptotic effects of oncolytic reovirus have been reported to be dependent on the presence of an activated RAS pathway in several solid tumor types. However, the mechanisms of selective anticancer efficacy of the reovirus-based formulation for cancer therapy (Reolysin, pelareorep) have not been rigorously studied in soft tissue sarcomas (STS). Here we report that Reolysin triggered a striking induction of the anti-angiogenic chemokine interferon-γ-inducible protein 10 (IP-10)/CXCL10 (CXC chemokine ligand 10) in both wild type and RAS mutant STS cells...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156049/management-of-pregnant-women-and-children-focusing-on-preventing-mother-to-infant-transmission
#7
Huey-Ling Chen, Wan-Hsin Wen, Mei-Hwei Chang
Hepatitis B virus (HBV) immunization has been effectively preventing chronic HBV infection with >90% efficacy in countries with universal neonatal immunization. Perinatal mother-to-infant transmission of HBV remains the major cause of chronic HBV infection despite immunization. Maternal hepatitis B e-antigen (HBeAg) and high viral load have been noted to be the most important risk factors for transmission. In recent years, short-term antiviral therapy for pregnant women in the third trimester has been shown to be highly effective in reducing 90% of vaccine failure in children...
November 16, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29156046/toward-a-cure-for-hepatitis-b-virus-infection-combination-therapy-involving-viral-suppression-and-immune-modulation-and-long-term-outcome
#8
Di Wu, Qin Ning
Chronic hepatitis B virus (HBV) infection remains a major global health burden. Currently, the approved therapeutic regimens include nucleos(t)ide analogues (NAs) and either interferon or pegylated interferon. NA therapy is generally safe and well tolerated, but the rate of posttreatment virologic relapse is high, making NA treatment a lifetime commitment. The benefits of pegylated interferon treatment include a finite duration, more-durable response and absence of viral resistance. However, sustained response to interferon alone is achieved only in a minority of patients, and side effects are common, which limit its clinical use...
November 16, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29155139/the-generation-and-characterisation-of-neutralising-antibodies-against-the-theiler-s-murine-encephalomyelitis-virus-tmev-gdvii-capsid-reveals-the-potential-binding-site-of-the-host-cell-co-receptor-heparan-sulfate
#9
Nicole Upfold, Caroline Ross, Özlem Tastan Bishop, Garry A Luke, Caroline Knox
The early stages of picornavirus capsid assembly and the host factors involved are poorly understood. Since the localisation of viral proteins in infected cells can provide information on their function, antibodies against purified Theiler's murine encephalomyelitis virus (TMEV) GDVII capsids were generated by immunisation of rabbits. The resultant anti-TMEV capsid antibodies recognised a C-terminal region of VP1 but not VP2 or VP3 by Western analysis. Examination of the sites of TMEV capsid assembly by indirect immunofluorescence and confocal microscopy showed that at 5hours post infection, capsid signal was diffusely cytoplasmic with strong perinuclear staining and moved into large punctate structures from 6 to 8hours post infection...
November 16, 2017: Virus Research
https://www.readbyqxmd.com/read/29154369/hepatitis-e-virus-infection
#10
REVIEW
Nassim Kamar, Jacques Izopet, Nicole Pavio, Rakesh Aggarwal, Alain Labrique, Heiner Wedemeyer, Harry R Dalton
Hepatitis E virus (HEV) infection can lead to acute and chronic hepatitis as well as to extrahepatic manifestations such as neurological and renal disease; it is the most common cause of acute viral hepatitis worldwide. Four genotypes are responsible for most infection in humans, of which HEV genotypes 1 and 2 are obligate human pathogens and HEV genotypes 3 and 4 are mostly zoonotic. Until quite recently, HEV was considered to be mainly responsible for epidemics of acute hepatitis in developing regions owing to contamination of drinking water supplies with human faeces...
November 16, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/29152054/structure-optimization-of-aloperine-derivatives-as-hiv-1-entry-inhibitors
#11
Zhao Dang, Hua Xie, Lei Zhu, Qingye Zhang, Zhijun Li, Li Huang, Chin-Ho Chen
As a step toward developing novel anti-HIV agents, we have identified a class of quinolizidines, including aloperine, that inhibit HIV at 1-5 μM by blocking viral entry. In this study, we have optimized the structure of aloperine and derived compounds with markedly improved activity. Our structural optimization has yielded an aloperine derivative 19 with approximately a 15-fold increase in anti-HIV-1 activity. Our mechanism of action study reveals that compound 19 does not inhibit binding of HIV-1 to receptors but arrests the virus from fusion with the membrane...
November 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29152052/discovery-of-thiophene-3-2-d-pyrimidine-derivatives-as-potent-hiv-1-nnrtis-targeting-the-tolerant-region-i-of-nnibp
#12
Dongwei Kang, Xiao Ding, Gaochan Wu, Zhipeng Huo, Zhongxia Zhou, Tong Zhao, Da Feng, Zhao Wang, Ye Tian, Dirk Daelemans, Erik De Clercq, Christophe Pannecouque, Peng Zhan, Xinyong Liu
Our previous studies led us to conclude that thiophene[3,2-d]pyrimidine is a promising scaffold for diarylpyrimidine (DAPY)-type anti-HIV agents with potent activity against resistance-associated human immunodeficiency virus (HIV) variants (J. Med. Chem. 2016, 59, 7991-8007; J. Med. Chem. 2017, 60, 4424-4443). In the present study, we designed and synthesized a series of thiophenepyrimidine derivatives with various substituents in the right wing region of the structure with the aim of developing new interactions with the tolerant region I of the binding pocket of the HIV-1 non-nucleoside reverse transcriptase (NNRTI), and we evaluated their activity against a panel of mutant HIV-1 strains...
November 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29150641/repurposing-of-the-anti-malaria-drug-chloroquine-for-zika-virus-treatment-and-prophylaxis
#13
Sergey A Shiryaev, Pinar Mesci, Antonella Pinto, Isabella Fernandes, Nicholas Sheets, Sujan Shresta, Chen Farhy, Chun-Teng Huang, Alex Y Strongin, Alysson R Muotri, Alexey V Terskikh
One of the major challenges of the current Zika virus (ZIKV) epidemic is to prevent congenital foetal abnormalities, including microcephaly, following ZIKV infection of pregnant women. Given the urgent need for ZIKV prophylaxis and treatment, repurposing of approved drugs appears to be a viable and immediate solution. We demonstrate that the common anti-malaria drug chloroquine (CQ) extends the lifespan of ZIKV-infected interferon signalling-deficient AG129 mice. However, the severity of ZIKV infection in these mice precludes the study of foetal (vertical) viral transmission...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29150240/dichotomous-expression-of-tnf-superfamily-ligands-on-antigen-presenting-cells-controls-post-priming-anti-viral-cd4-t-cell-immunity
#14
Yu-Han Chang, Kuan Chung Wang, Kuan-Lun Chu, Derek L Clouthier, Anh T Tran, Miguel S Torres Perez, Angela C Zhou, Ali A Abdul-Sater, Tania H Watts
T cell antigen-presenting cell (APC) interactions early during chronic viral infection are crucial for determining viral set point and disease outcome, but how and when different APC subtypes contribute to these outcomes is unclear. The TNF receptor superfamily (TNFRSF) member GITR is important for CD4(+) T cell accumulation and control of chronic lymphocytic choriomeningitis virus (LCMV). We found that type I interferon (IFN-I) induced TNFSF ligands GITRL, 4-1BBL, OX40L, and CD70 predominantly on monocyte-derived APCs and CD80 and CD86 predominantly on classical dendritic cells (cDCs)...
November 13, 2017: Immunity
https://www.readbyqxmd.com/read/29150085/pinocembrin-alleviates-cognition-deficits-by-inhibiting-inflammation-in-diabetic-mice
#15
Bing Pei, Jian Sun
Diabetic encephalopathy (DE) is one of the most common diabetic complications in diabetes mellitus and is characterized by cognitive impairment and neuroinflammation. It has been reported that hyperglycemia can induce hippocampal and cortical neuronal damage, which can result in severe spatial learning and memory impairment. Pinocembrin (Pino) has been widely used in the therapy of cancer and other diseases due to its anti-inflammatory, anti-allergic, anti-oxidant, anti-carcinogenic, and anti-viral activities...
November 8, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29149973/hepatitis-c-virus-recurrence-occurs-earlier-in-patients-receiving-donation-after-circulatory-death-liver-transplant-grafts-compared-with-those-receiving-donation-after-brainstem-death-grafts
#16
S A Townsend, M A Monga, P Nightingale, D Mutimer, A M Elsharkawy, A Holt
INTRODUCTION: Hepatitis C virus (HCV)-related cirrhosis remains the commonest indication for liver transplantation worldwide, yet few studies have investigated the impact of donation after circulatory death (DCD) graft use on HCV recurrence and patient outcomes. DCD grafts have augmented the limited donor organ pool and reduced wait-list mortality, although concerns regarding graft longevity and patient outcome persist. METHODS: This was a single-center study of all HCV + adults who underwent DCD liver transplantation between 2004 and 2014...
November 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/29149077/rna-virus-evolution-via-a-quasispecies-based-model-reveals-a-drug-target-with-a-high-barrier-to-resistance
#17
Richard J Bingham, Eric C Dykeman, Reidun Twarock
The rapid occurrence of therapy-resistant mutant strains provides a challenge for anti-viral therapy. An ideal drug target would be a highly conserved molecular feature in the viral life cycle, such as the packaging signals in the genomes of RNA viruses that encode an instruction manual for their efficient assembly. The ubiquity of this assembly code in RNA viruses, including major human pathogens, suggests that it confers selective advantages. However, their impact on viral evolution cannot be assessed in current models of viral infection that lack molecular details of virus assembly...
November 17, 2017: Viruses
https://www.readbyqxmd.com/read/29147793/pharmacophoric-characteristics-of-dengue-virus-ns2b-ns3pro-inhibitors-a-systematic-review-of-the-most-promising-compounds
#18
REVIEW
Camyla Alves Leonel, William Gustavo Lima, Michelli Dos Santos, Ariane Coelho Ferraz, Alex Gutterres Taranto, José Carlos de Magalhães, Luciana Lara Dos Santos, Jaqueline Maria Siqueira Ferreira
Dengue virus (DENV) infection can lead to a wide range of clinical manifestations, including fatal hemorrhagic complications. There is a need to find effective pharmacotherapies to treat this disease due to the lack of specific immunotherapies and antiviral drugs. That said, the DENV NS2B/NS3pro protease complex is essential in both the viral multiplication cycle and in disease pathogenesis, and is considered a promising target for new antiviral therapies. Here, we performed a systematic review to evaluate the pharmacophoric characteristics of promising compounds against NS2B/NS3pro reported in the past 10 years...
November 16, 2017: Archives of Virology
https://www.readbyqxmd.com/read/29146961/identification-of-host-dead-box-rna-helicases-that-regulate-cellular-tropism-of-oncolytic-myxoma-virus-in-human-cancer-cells
#19
Masmudur M Rahman, Eugenie Bagdassarian, Mohamed A M Ali, Grant McFadden
Myxoma virus (MYXV), a Leporipoxvirus, is being developed as an oncolytic virotherapeutic for the treatment of a variety of human cancers. MYXV tropism for human cancer cells is largely mediated by intracellular signaling networks that regulate viral replication or innate antiviral response pathways. Thus, MYXV is fully or partially permissive for the majority of human cancer cells that harbor defects in antiviral signaling, but a minority are nonpermissive because the virus infection aborts before its completion...
November 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29146616/therapeutic-potential-of-afatinib-for-cancers-with-erbb2-her2-transmembrane-domain-mutations-g660d-and-v659e
#20
Hiromasa Yamamoto, Shinichi Toyooka, Takashi Ninomiya, Shigemi Matsumoto, Masashi Kanai, Shuta Tomida, Katsuyuki Kiura, Manabu Muto, Ken Suzawa, Patrice Desmeules, Mark G Kris, Bob T Li, Marc Ladanyi
We previously reported on a family with hereditary lung cancer, in which a germline mutation in the transmembrane domain (G660D) of avian erythroblastic leukemia viral oncogene homolog 2 (erb-b2 receptor tyrosine kinase 2) (ERBB2; human epidermal growth factor receptor 2 [HER2]) seemed to be responsible for the cancer predisposition. Although few data are available on treatment, anti-ERBB2 therapeutic agents may be effective for ERBB2-mutant cancers. The familial lung cancer patient in one of the authors' institutes developed bone metastasis with enlarging lung tumors and was treated with the ERBB2 inhibitor afatinib...
November 16, 2017: Oncologist
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