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https://www.readbyqxmd.com/read/29458131/inhibition-of-hepatitis-b-virus-replication-via-hbv-dna-cleavage-by-cas9-from-staphylococcus-aureus
#1
Yu Liu, Miaoxian Zhao, Mingxing Gong, Ying Xu, Cantao Xie, Haohui Deng, Xueying Li, Hongkai Wu, Zhanhui Wang
Chronic hepatitis B virus (HBV) infection is difficult to cure due to the presence of covalently closed circular DNA (cccDNA). Accumulating evidence indicates that the CRISPR/Cas9 system effectively disrupts HBV genome, including cccDNA, in vitro and in vivo. However, efficient delivery of CRISPR/Cas9 system to the liver or hepatocytes using an adeno-associated virus (AAV) vector remains challenging due to the large size of Cas9 from Streptococcus pyogenes (Sp). The recently identified Cas9 protein from Staphylococcus aureus (Sa) is smaller than SpCas9 and thus is able to be packaged into the AAV vector...
February 16, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29458052/regulation-of-proliferation-and-functioning-of-transplanted-cells-by-using-herpes-simplex-virus-thymidine-kinase-gene-in-mice
#2
Mari Tsujimura, Kosuke Kusamori, Chihiro Oda, Airi Miyazaki, Hidemasa Katsumi, Toshiyasu Sakane, Makiya Nishikawa, Akira Yamamoto
Though cell transplantation is becoming an attractive therapeutic method, uncontrolled cell proliferation or overexpression of cellular functions could cause adverse effects. These unfavorable outcomes could be avoided by regulating the proliferation or functioning of transplanted cells. In this study, we used a combination of the herpes simplex virus thymidine kinase (HSVtk) gene, a suicide gene, and ganciclovir (GCV) to control the proliferation and functioning of insulin-secreting cells after transplantation in diabetic mice...
February 16, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29458021/increased-mortality-from-influenza-infection-in-long-chain-acyl-coa-dehydrogenase-knockout-mice
#3
Apurva Shinde, Jiadi Luo, Sivakama S Bharathi, Huifang Shi, Megan E Beck, Kevin J McHugh, John F Alcorn, Jieru Wang, Eric S Goetzman
We previously showed that the mitochondrial fatty acid oxidation enzyme long-chain acyl-CoA dehydrogenase (LCAD) is expressed in alveolar type II pneumocytes and that LCAD-/- mice have altered breathing mechanics and surfactant defects. Here, we hypothesized that LCAD-/- mice would be susceptible to influenza infection. Indeed, LCAD-/- mice demonstrated increased mortality following infection with 2009 pandemic influenza (A/CA/07/09). However, the mortality was not due to increased lung injury, as inflammatory cell counts, viral titers, and histology scores all showed non-significant trends toward milder injury in LCAD-/- mice...
February 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29458009/the-lim-only-protein-fhl2-supports-influenza-a-virus-induced-lung-inflammation-by-restricting-the-host-adaptive-immune-response
#4
Dörthe Masemann, Rafael Leite Dantas, Siarhei Sitnik, Tanja Schied, Carolin Nordhoff, Stephan Ludwig, Viktor Wixler
FHL2 is a multifunctional adaptor protein with fine-tuning adjustment properties. It acts as a regulator of signaling cascades but also as a cofactor of transcription and controls several anti-inflammatory immune responses. Recently, we described FHL2 as a novel regulator of influenza A virus propagation. We have shown that in vitro FHL2 restricts viral replication by accelerating the IRF-3-dependent transcription of the Ifnb1 gene. In this work, we unraveled an ambiguous role of FHL2 during influenza A virus infection in vivo...
February 16, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29457711/small-animal-models-for-evaluating-filovirus-countermeasures
#5
Logan Banadyga, Gary Wong, Xiangguo Qiu
The development of novel therapeutics and vaccines to treat or prevent disease caused by filoviruses, such as Ebola and Marburg viruses, depends on the availability of animal models that faithfully recapitulate clinical hallmarks of disease as it is observed in humans. In particular, small animal models (like mice and guinea pigs) are historically and frequently used for the primary evaluation of antiviral countermeasures, prior to testing in nonhuman primates, which represent the gold-standard filovirus animal model...
February 19, 2018: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29456794/discovery-of-3-3-spiro-azetidine-2-oxo-indoline-derivatives-as-fusion-inhibitors-for-treatment-of-rsv-infection
#6
Weihua Shi, Zhigan Jiang, Haiying He, Fubiao Xiao, Fusen Lin, Ya Sun, Lijuan Hou, Liang Shen, Lixia Han, Minggao Zeng, Kunmin Lai, Zhengxian Gu, Xinsheng Chen, Tao Zhao, Li Guo, Chun Yang, Jian Li, Shuhui Chen
A new series of 3,3'-spirocyclic-2-oxo-indoline derivatives was synthesized and evaluated against respiratory syncytial virus (RSV) in a cell-based assay and animal model. Extensive structure-activity relationship study led to a lead compound 14h , which exhibited excellent in vitro potency with an EC50 value of 0.8 nM and demonstrated 71% oral bioavailability in mice. In a mouse challenge model of RVS infection, 14h demonstrated superior efficacy with a 3.9log RSV virus load reduction in the lung following an oral dose of 50 mg/kg...
February 8, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29456016/monoclonal-antibody-based-in-vitro-potency-assay-as-a-predictor-of-antigenic-integrity-and-in-vivo-immunogenicity-of-a-respiratory-syncytial-virus-post-fusion-f-protein-based-vaccine
#7
Matieyendou Didier Djagbare, Li Yu, Arun Parupudi, Jenny Sun, Melissa L Coughlin, Benjamin S Rush, Gautam Sanyal
The post-fusion form of Respiratory Syncytial Virus (RSV) fusion (F) protein has been used recently in clinical trials as a potential vaccine antigen with the objective of eliciting protective immune response against RSV. In this paper, in vitro antigenicity and in vivo immunogenicity of recombinant, soluble F protein of RSV (RSVsF) were evaluated by several assays. In Vitro Relative Potency (IVRP) of RSVsF was measured in a sandwich ELISA using two antibodies, each specific for epitope site A or C. Therefore, IVRP reflected the integrity of the antigen in terms of changes in antibody binding affinity of either or both of these sites...
February 15, 2018: Vaccine
https://www.readbyqxmd.com/read/29455203/absence-of-nicotinamide-nucleotide-transhydrogenase-in-c57bl-6j-mice-exacerbates-experimental-atherosclerosis
#8
Aimee E Vozenilek, Matthew Vetkoetter, Jonette M Green, Xinggui Shen, James G Traylor, Ronald L Klein, A Wayne Orr, Matthew D Woolard, David M Krzywanski
BACKGROUND: Mitochondrial reactive oxygen species (ROS) contribute to inflammation and vascular remodeling during atherosclerotic plaque formation. C57BL/6N (6N) and C57BL/6J (6J) mice display distinct mitochondrial redox balance due to the absence of nicotinamide nucleotide transhydrogenase (NNT) in 6J mice. We hypothesize that differential NNT expression between these animals alters plaque development. METHODS: 6N and 6J mice were treated with AAV8-PCSK9 (adeno-associated virus serotype 8/proprotein convertase subtilisin/kexin type 9) virus leading to hypercholesterolemia, increased low-density lipoprotein, and atherosclerosis in mice fed a high-fat diet (HFD)...
February 16, 2018: Journal of Vascular Research
https://www.readbyqxmd.com/read/29454797/alterations-in-intestinal-microbiota-lead-to-production-of-interleukin-17-by-intrahepatic-%C3%AE-%C3%AE-t-cell-receptor-positive-cells-and-pathogenesis-of-cholestatic-liver-disease
#9
Dana Tedesco, Manoj Thapa, Chui-Yoke Chin, Yong Ge, Minghao Gong, Jing Li, Sanjeev Gumber, Patrick Speck, Elizabeth J Elrod, Eileen M Burd, William H Kitchens, Joseph F Magliocca, Andrew B Adams, David S Weiss, Mansour Mohamadzadeh, Arash Grakoui
BACKGROUND & AIMS: Variants at the ATP binding cassette subfamily B member 4 gene (ABCB4 or MDR2) locus, which encodes a biliary transport protein, are associated with a spectrum of cholestatic liver diseases. Exacerbation of liver disease has been linked to increased hepatic levels of interleukin 17 (IL17), yet the mechanisms of this increase are not understood. We studied mice with disruption of Mdr2 to determine how defects in liver and alteration in the microbiota contribute to production of IL17 by intrahepatic γδ T cells...
February 15, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29454522/genetic-and-subunit-vaccines-based-on-the-stem-domain-of-the-equine-influenza-hemagglutinin-provide-homosubtypic-protection-against-heterologous-strains
#10
Lorena Itatí Ibañez, Cecilia Andrea Caldevilla, Yesica Paredes Rojas, Nora Mattion
H3N8 influenza virus strains have been associated with infectious disease in equine populations throughout the world. Although current vaccines for equine influenza stimulate a protective humoral immune response against the surface glycoproteins, disease in vaccinated horses has been frequently reported, probably due to poor induction of cross-reactive antibodies against non-matching strains. This work describes the performance of a recombinant protein vaccine expressed in prokaryotic cells (ΔHAp) and of a genetic vaccine (ΔHAe), both based on the conserved stem region of influenza hemagglutinin (HA) derived from A/equine/Argentina/1/93 (H3N8) virus...
February 15, 2018: Vaccine
https://www.readbyqxmd.com/read/29454517/intradermal-immunization-with-inactivated-swine-influenza-virus-and-adjuvant-polydi-sodium-carboxylatoethylphenoxy-phosphazene-pcep-induced-humoral-and-cell-mediated-immunity-and-reduced-lung-viral-titres-in-pigs
#11
Royford Magiri, Ken Lai, Alyssa Chaffey, Yan Zhou, Hyun-Mi Pyo, Volker Gerdts, Heather L Wilson, George Mutwiri
Swine influenza virus is endemic worldwide and it is responsible for significant economic losses to the swine industry. A vaccine that stimulates a rapid and long-lasting protective immune response to prevent this infection is highly sought. Poly[di(sodium carboxylatoethylphenoxy)-phosphazene (PCEP) has demonstrated adjuvant activity when formulated as part of multiple vaccines in mice and pigs. In this study we examined the magnitude and type of immune response induced in pigs vaccinated via the intramuscular or intradermal routes with inactivated swine influenza virus (SIV) H1N1 vaccine formulated with PCEP...
February 14, 2018: Vaccine
https://www.readbyqxmd.com/read/29453985/zika-virus-infected-primary-microglia-impairs-npcs-proliferation-and-differentiation
#12
Jin Wang, Jing Liu, Rui Zhou, Xin Ding, Qipeng Zhang, Chenyu Zhang, Liang Li
Zika virus (ZIKV) can lead to severe birth defects especially microcephaly in newborns by infecting human neural progenitors and impairing brain development. However, as the resident immune cells in the brain, the role of microglia in the ZIKV pathology is not clearly defined. To understand the interplay between immune response and neural cells, we investigate the interaction between microglia and NPCs during ZIKV infection. Our results demonstrate that primary microglia infected with ZIKV induces an inflammatory response similar to that in human, producing high level of tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), interleukin 1β (IL-1β) and inducible nitric oxide synthase (iNOS)...
February 14, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29453308/sex-specific-mechanisms-of-resistance-vessel-endothelial-dysfunction-induced-by-cardiometabolic-risk-factors
#13
Ana P Davel, Qing Lu, M Elizabeth Moss, Sitara Rao, Imran J Anwar, Jennifer J DuPont, Iris Z Jaffe
BACKGROUND: The incidence of obesity is rising, particularly among women. Microvascular dysfunction is more common with female sex, obesity, and hyperlipidemia and predicts adverse cardiovascular outcomes, but the molecular mechanisms are unclear. Because obesity is associated with mineralocorticoid receptor (MR) activation, we tested the hypothesis that MR in endothelial cells contribute to sex differences in resistance vessel dysfunction in response to cardiometabolic risk factors. METHODS AND RESULTS: Male and female endothelial cell-specific MR knockout mice and MR-intact littermates were randomized to high-fat-diet-induced obesity or obesity with hyperlipidemia induced by adeno-associated virus-based vector targeting transfer of the mutant stable form (DY mutation) of the human PCSK9 (proprotein convertase subtilisin/kexin type 9) gene and compared with control diet...
February 16, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29452594/comparative-immunogenicity-of-preparations-of-yeast-derived-dengue-oral-vaccine-candidate
#14
Jyotiranjan Bal, Nguyen Ngoc Luong, Jisang Park, Ki-Duk Song, Yong-Suk Jang, Dae-Hyuk Kim
BACKGROUND: Dengue is listed as a neglected tropical disease by the Center for Disease Control and Preservation, as there are insufficient integrated surveillance strategies, no effective treatment, and limited licensed vaccines. Consisting of four genetically distinct serotypes, dengue virus (DENV) causes serious life-threatening infections due to its complexity. Antibody-dependent enhancement by pre-existing cross-reactive as well as homotypic antibodies further worsens the clinical symptoms of dengue...
February 16, 2018: Microbial Cell Factories
https://www.readbyqxmd.com/read/29451705/modeling-asthma-pitfalls-promises-and-the-road-ahead
#15
REVIEW
Helene F Rosenberg, Kirk M Druey
Asthma is a chronic, heterogeneous, and recurring inflammatory disease of the lower airways, with exacerbations that feature airway inflammation and bronchial hyperresponsiveness. Asthma has been modeled extensively via disease induction in both wild-type and genetically manipulated laboratory mice (Mus musculus). Antigen sensitization and challenge strategies have reproduced numerous important features of airway inflammation characteristic of human asthma, notably the critical roles of type 2 T helper cell cytokines...
February 16, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29450905/a-tramp-derived-orthotopic-prostate-syngeneic-tops-cancer-model-for-investigating-anti-tumor-treatments
#16
Justin Lardizabal, Jun Ding, Zahid Delwar, Paul S Rennie, William Jia
BACKGROUND: Patients with advanced prostate cancer have limited curative options, therefore new treatments are needed. Mouse models play a pivotal role in the discovery and development of new treatments. In the present study, a TRAMP-derived Orthotopic Prostate Syngeneic (TOPS) mouse model was developed and found to provide a consistent means of monitoring tumor and metastatic responses to novel treatments. METHODS: The mouse TOPS model was generated using luciferase transduced TRAMP-C2 prostate cancer cells that were orthotopically injected into Bl6 mice by ultrasound guidance...
February 16, 2018: Prostate
https://www.readbyqxmd.com/read/29449555/intravenous-injections-of-the-oncolytic-virus-m1-as-a-novel-therapy-for-muscle-invasive-bladder-cancer
#17
Cheng Hu, Ying Liu, Yuan Lin, Jian-Kai Liang, Wen-Wen Zhong, Ke Li, Wen-Tao Huang, De-Juan Wang, Guang-Mei Yan, Wen-Bo Zhu, Jian-Guang Qiu, Xin Gao
Muscle-invasive bladder cancer (MIBC) is associated with low survival and high recurrence rates even in cases in which patients receive systemic treatments, such as surgery and chemotherapy. Here, we found that a naturally existing alphavirus, namely, M1, selectively kills bladder cancer cells but not normal cells, findings supported by our observations of changes in viral replication and MIBC and patient-derived MIBC cell apoptosis. Transcriptome analysis revealed that interferon-stimulated genes (ISGs) are expressed at low levels in sensitive bladder cancer cells and high levels in resistant cells...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449536/impaired-autophagic-flux-is-associated-with-the-severity-of-trauma-and-the-role-of-a-2a-r-in-brain-cells-after-traumatic-brain-injury
#18
Xu-Jia Zeng, Ping Li, Ya-Lei Ning, Yan Zhao, Yan Peng, Nan Yang, Zi-Ai Zhao, Jiang-Fan Chen, Yuan-Guo Zhou
Recent studies have shown that after traumatic brain injury (TBI), the number of autophagosomes is markedly increased in brain cells surrounding the wound; however, whether autophagy is enhanced or suppressed by TBI remains controversial. In our study, we used a controlled cortical impact system to establish models of mild, moderate and severe TBI. In the mild TBI model, the levels of autophagy-related protein 6 (Beclin1) and autophagy-related protein 12 (ATG12)-autophagy-related protein 5 (ATG5) conjugates were increased, indicating the enhanced initiation of autophagy...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29447858/intrathecal-injection-of-scaav9-higf1-prolongs-the-survival-of-als-model-mice-by-inhibiting-the-nf-kb-pathway
#19
HaoJie Hu, HuiQian Lin, WeiSong Duan, Can Cui, ZhongYao Li, YaKun Liu, Wan Wang, Di Wen, Ying Wang, ChunYan Li
Amyotrophic lateral sclerosis (ALS) is a chronic, fatal neurodegenerative disorder characterized by the progressive loss of upper and lower motor neurons. Currently, there is no effective drug for ALS. Recent studies in ALS model mice have shown that insulin-like growth factor-1 (IGF1) may be a promising therapeutic drug. We demonstrate that self-complementary adeno-associated virus serum type 9 encoding the human IGF1 (scAAV9-hIGF1) could significantly postpone the onset and slow down the progression of the disease owning to inhibiting the NF-κB signalling pathway...
February 12, 2018: Neuroscience
https://www.readbyqxmd.com/read/29447697/herpes-simplex-virus-1-vp22-inhibits-aim2-dependent-inflammasome-activation-to-enable-efficient-viral-replication
#20
Yuhei Maruzuru, Takeshi Ichinohe, Ryota Sato, Kensuke Miyake, Tokuju Okano, Toshihiko Suzuki, Takumi Koshiba, Naoto Koyanagi, Shumpei Tsuda, Mizuki Watanabe, Jun Arii, Akihisa Kato, Yasushi Kawaguchi
The AIM2 inflammasome is activated by DNA, leading to caspase-1 activation and release of pro-inflammatory cytokines interleukin 1β (IL-1β) and IL-18, which are critical mediators in host innate immune responses against various pathogens. Some viruses employ strategies to counteract inflammasome-mediated induction of pro-inflammatory cytokines, but their in vivo relevance is less well understood. Here we show that the herpes simplex virus 1 (HSV-1) tegument protein VP22 inhibits AIM2-dependent inflammasome activation...
February 14, 2018: Cell Host & Microbe
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