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https://www.readbyqxmd.com/read/28545059/uggt1-enhances-enterovirus-71-pathogenicity-by-promoting-viral-rna-synthesis-and-viral-replication
#1
Peng-Nien Huang, Jia-Rong Jheng, Jamie J Arnold, Jen-Ren Wang, Craig E Cameron, Shin-Ru Shih
Positive-strand RNA virus infections can induce the stress-related unfolded protein response (UPR) in host cells. This study found that enterovirus A71 (EVA71) utilizes host UDP-glucose glycoprotein glucosyltransferase 1 (UGGT1), a key endoplasmic reticulum protein (ER) involved in UPR, to enhance viral replication and virulence. EVA71 forms replication complexes (RCs) on cellular membranes that contain a mix of host and viral proteins to facilitate viral replication, but the components and processes involved in the assembly and function of RCs are not fully understood...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28544850/pcpp-adjuvanted-respiratory-syncytial-virus-rsv-sf-subunit-vaccine-self-assembled-supramolecular-complexes-enable-enhanced-immunogenicity-and-protection
#2
Corinne Cayatte, Alexander Marin, Gaurav Manohar Rajani, Kirsten Schneider-Ohrum, Angie Snell Bennett, Jason D Marshall, Alexander K Andrianov
PCPP, a well-defined polyphosphazene macromolecule, has been studied as an immunoadjuvant for a soluble form of the post-fusion glycoprotein (RSV sF) of RSV, which is an attractive vaccine candidate for inducing RSV-specific immunity in mice and humans. We demonstrate that RSV sF-PCPP formulations induce high neutralization titers to RSV comparable to Alum formulations even at a low PCPP dose and protect animals against viral challenge both in the lung and upper respiratory tract. PCPP formulations were also characterized by Th1-biased responses, compared to Th2-biased responses that are more typical for RSV sF alone or RSV sF-Alum formulations, suggesting an inherent immunostimulating activity of the polyphosphazene adjuvant...
May 25, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28542569/fas-associated-factor-1-positively-regulates-type-i-interferon-response-to-rna-virus-infection-by-targeting-nlrx1
#3
Jae-Hoon Kim, Min-Eun Park, Chamilani Nikapitiya, Tae-Hwan Kim, Md Bashir Uddin, Hyun-Cheol Lee, Eunhee Kim, Jin Yeul Ma, Jae U Jung, Chul-Joong Kim, Jong-Soo Lee
FAS-associated factor-1 (FAF1) is a component of the death-inducing signaling complex involved in Fas-mediated apoptosis. It regulates NF-κB activity, ubiquitination, and proteasomal degradation. Here, we found that FAF1 positively regulates the type I interferon pathway. FAF1gt/gt mice, which deficient in FAF1, and FAF1 knockdown immune cells were highly susceptible to RNA virus infection and showed low levels of inflammatory cytokines and type I interferon (IFN) production. FAF1 was bound competitively to NLRX1 and positively regulated type I IFN signaling by interfering with the interaction between NLRX1 and MAVS, thereby freeing MAVS to bind RIG-I, which switched on the MAVS-RIG-I-mediated antiviral signaling cascade...
May 22, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28542275/combination-of-the-immunization-with-the-sequence-close-to-the-consensus-sequence-and-two-dna-prime-plus-one-vlp-boost-generate-h5-hemagglutinin-specific-broad-neutralizing-antibodies
#4
Guiqin Wang, Renfu Yin, Paul Zhou, Zhuang Ding
Hemagglutinin (HA) head has long been considered to be able to elicit only a narrow, strain-specific antibody response as it undergoes rapid antigenic drift. However, we previously showed that a heterologous prime-boost strategy, in which mice were primed twice with DNA encoding HA and boosted once with virus-like particles (VLP) from an H5N1 strain A/Thailand/1(KAN)-1/2004 (noted as TH DDV), induced anti-head broad cross-H5 neutralizing antibody response. To explain why TH DDV immunization could generate such breadth, we systemically compared the neutralization breadth and potency between TH DDV sera and immune sera elicited by TH DDD (three times of DNA immunizations), TH VVV (three times of VLP immunizations), TH DV (one DNA prime plus one VLP boost) and TK DDV (plasmid DNA and VLP derived from another H5N1 strain, A/Turkey/65596/2006)...
2017: PloS One
https://www.readbyqxmd.com/read/28540728/sulfonation-disposition-of-acacetin-in-vitro-and-in-vivo
#5
Qisong Zhang, Lijun Zhu, Xia Gong, Yanjiao Ruan, Jia Yu, Huangyu Jiang, Ying Wang, Xiaoxiao Qi, Linlin Lu, Zhong Qiu Liu
Acacetin, an important component of acacia honey, exerts extensive therapeutic effects on many cancers. However, sulfonation disposition of acacetin has rarely been reported. Therefore, this study aims to investigate the sulfonation disposition of acacetin systematically. Results showed that acacetin-7-sulfate was the main metabolite mediated primarily by sulfotransferases (SULT) 1A1. Dog liver S9 presented the highest formation rate of acacetin-7-sulfate. Compared with that in wild-type Friend Virus B (FVB) mice, plasma exposure of acacetin-7-sulfate decreased significantly in multiple drug resistance protein 1 knockout (Mrp1-/-) mice, while increased evidently in breast cancer resistance protein knockout (Bcrp-/-) mice...
May 25, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28539661/the-pb2-mutation-with-lysine-at-627-enhances-the-pathogenicity-of-avian-influenza-h7n9-virus-which-belongs-to-a-non-zoonotic-lineage
#6
Weixuan Li, Horace Hok Yeung Lee, Run Feng Li, Huachen Maria Zhu, Guan Yi, Joseph Sriyal Malik Peiris, Zi Feng Yang, Chris Ka Pun Mok
A novel avian-origin influenza A (H7N9) virus emerged in China in 2013 and has caused zoonotic disease in over 1123 persons with an overall mortality around 30%. Amino acid changes at the residues 591, 627 and 701 of polymerase basic protein 2 (PB2) have been found frequently in the human H7N9 isolates but not in viruses isolated from avian species. We have recently identified a cluster of H7N9 viruses in ducks which circulated in China prior to the first recognition of zoonotic disease in 2013. These duck viruses have genetic background distinct from the zoonotic H7N9 lineage...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28539639/the-absence-of-interferon-%C3%AE-promotor-stimulator-1-ips-1-predisposes-to-bronchiolitis-and-asthma-like-pathology-in-response-to-pneumoviral-infection-in-mice
#7
Jennifer Simpson, Jason P Lynch, Zhixuan Loh, Vivian Zhang, Rhiannon B Werder, Kirsten Spann, Simon Phipps
Respiratory syncytial virus (RSV)-bronchiolitis is a major cause of infant morbidity and mortality and a risk factor for subsequent asthma. We showed previously that toll-like receptor (TLR)7 in plasmacytoid dendritic cells (pDCs) is critical for protection against bronchiolitis and asthma in mice infected with pneumonia virus of mice (PVM), the mouse homolog of RSV. This lack of redundancy was unexpected as interferon-β promotor stimulator-1 (IPS-1) signalling, downstream of RIG-I-like receptor (RLR) and not TLR7 activation, contributes to host defence in hRSV-inoculated adult mice...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28539439/contribution-of-human-lung-parenchyma-and-leukocyte-influx-to-oxidative-stress-and-immune-mediated-pathology-following-nipah-infection
#8
Olivier Escaffre, Tais B Saito, Terry L Juelich, Tetsuro Ikegami, Jennifer K Smith, David D Perez, Colm Atkins, Corri B Levine, Matthew B Huante, Rebecca J Nusbaum, Janice J Endsley, Alexander N Freiberg, Barry Rockx
Nipah virus (NiV) is a zoonotic emerging paramyxovirus that can cause a fatal respiratory illness or encephalitis in humans. Despite many efforts, the molecular mechanisms of NiV-induced acute lung injury (ALI) remain unclear. We previously showed that NiV replicates to high titers in human lung grafts in NOD scid gamma mice, resulting in a robust inflammatory response. Interestingly, these mice can undergo human immune system reconstitution by the Bone marrow, Liver, and Thymus (BLT) reconstitution method, in addition to lung tissue engraftment, giving altogether a realistic model to study human respiratory viral infections...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28538182/targeting-metabolic-reprogramming-by-influenza-infection-for-therapeutic-intervention
#9
Heather S Smallwood, Susu Duan, Marie Morfouace, Svetlana Rezinciuc, Barry L Shulkin, Anang Shelat, Erika E Zink, Sandra Milasta, Resha Bajracharya, Ajayi J Oluwaseum, Martine F Roussel, Douglas R Green, Ljiljana Pasa-Tolic, Paul G Thomas
Influenza is a worldwide health and financial burden posing a significant risk to the immune-compromised, obese, diabetic, elderly, and pediatric populations. We identified increases in glucose metabolism in the lungs of pediatric patients infected with respiratory pathogens. Using quantitative mass spectrometry, we found metabolic changes occurring after influenza infection in primary human respiratory cells and validated infection-associated increases in c-Myc, glycolysis, and glutaminolysis. We confirmed these findings with a metabolic drug screen that identified the PI3K/mTOR inhibitor BEZ235 as a regulator of infectious virus production...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28537896/5t4-oncofoetal-glycoprotein-an-old-target-for-a-novel-prostate-cancer-immunotherapy
#10
Federica Cappuccini, Emily Pollock, Stephen Stribbling, Adrian V S Hill, Irina Redchenko
The tumour-associated antigen 5T4 is an attractive target for cancer immunotherapy. However to date, reported 5T4-specific cellular immune responses induced by various immunisation platforms have been largely weak or non-existent. In the present study, we have evaluated a heterologous prime boost regime based on the simian adenovirus ChAdOx1 and modified vaccinia virus Ankara (MVA) expressing 5T4 for immunogenicity and tumour protective efficacy in a mouse cancer model. Vaccination-induced immune responses were strong, durable and attributable primarily to CD8+ T cells...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537249/airway-t-cells-protect-against-rsv-infection-in-the-absence-of-antibody
#11
E Kinnear, L Lambert, J U McDonald, H M Cheeseman, L J Caproni, J S Tregoning
Tissue resident memory T (Trm) cells act as sentinels and early responders to infection. Respiratory syncytial virus (RSV)-specific Trm cells have been detected in the lungs after human RSV infection, but whether they have a protective role is unknown. To dissect the protective function of Trm cells, BALB/c mice were infected with RSV; infected mice developed antigen-specific CD8(+) Trm cells (CD103(+)/CD69(+)) in the lungs and airways. Intranasally transferring cells from the airways of previously infected animals to naïve animals reduced weight loss on infection in the recipient mice...
May 24, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28536674/anti-idiotypic-antibodies-specific-to-prm-monoantibody-prevent-antibody-dependent-enhancement-of-dengue-virus-infection
#12
Miao Wang, Fan Yang, Dana Huang, Yalan Huang, Xiaomin Zhang, Chao Wang, Shaohua Zhang, Renli Zhang
Dengue virus (DENV) co-circulates as four serotypes (DENV1-4). Primary infection only leads to self-limited dengue fever. But secondary infection with another serotype carries a higher risk of increased disease severity, causing life-threatening dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). Serotype cross-reactive antibodies facilitate DENV infection in Fc-receptor-bearing cells by promoting virus entry via Fcγ receptors (FcγR), a process known as antibody dependent enhancement (ADE). Most studies suggested that enhancing antibodies were mainly specific to the structural premembrane protein (prM) of DENV...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28534493/usp13-negatively-regulates-antiviral-responses-by-deubiquitinating-sting
#13
He Sun, Qiang Zhang, Ying-Ying Jing, Man Zhang, Hai-Ying Wang, Zeng Cai, Tianzi Liuyu, Zhi-Dong Zhang, Tian-Chen Xiong, Yan Wu, Qi-Yun Zhu, Jing Yao, Hong-Bing Shu, Dandan Lin, Bo Zhong
STING (also known as MITA) is critical for host defence against viruses and the activity of STING is regulated by ubiquitination. However, the deubiquitination of STING is not fully understood. Here, we show that ubiquitin-specific protease 13 (USP13) is a STING-interacting protein that catalyses deubiquitination of STING. Knockdown or knockout of USP13 potentiates activation of IRF3 and NF-κB and expression of downstream genes after HSV-1 infection or transfection of DNA ligands. USP13 deficiency results in impaired replication of HSV-1...
May 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28532813/genetics-and-biological-property-analysis-of-korea-lineage-of-influenza-a-h9n2-viruses
#14
Min Kang, Hyung-Kwan Jang
H9N2 influenza viruses have been detected from wild and domestic avian species including chickens and ducks worldwide. Few studies have compared the biological properties of different H9N2 lineages or determined whether certain lineages might pose a higher risk to mammals, especially H9N2 viruses of Korean lineage. The objective of this study was to characterize the genetic and biological properties of 22 Korean H9N2 viruses and assess their potential risks to mammals. Their complete genomes were analyzed. Some Korean H9N2 viruses were found to carry mammalian host-specific mutations...
May 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28532811/bovine-vaccinia-inactivated-vaccinia-virus-vaccine-induces-protection-in-murine-model
#15
Ana Carolina Diniz Matos, Maria Isabel Maldonado Coelho Guedes, Izabelle Silva Rehfeld, Erica Azevedo Costa, Aristoteles Gomes Costa, Natalia Lopes da Silva, Andrey Pereira Lage, Zélia Inês Portela Lobato
Bovine vaccinia (BV), caused by Vaccinia virus (VACV), is a zoonosis characterized by exanthematous lesions on the teats of dairy cows and the milkers' hands. Since 1999, due to the occurrence of many BV outbreaks in dairy farms across all Brazilian regions, there is a need to improve the control and prevention measures of the disease. Vaccination is one of the major tools to prevent viral diseases, and it could be an alternative for BV prevention. The main objective of this study was the development of vaccine formulations against BV using the inactivated VACV strain GP2 as antigen combined with different adjuvants...
May 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28532602/inactivation-of-west-nile-virus-in-serum-with-heat-ionic-detergent-and-reducing-agent-for-proteomic-applications
#16
Louis A Altamura, Lisa H Cazares, Susan R Coyne, James G Jaissle, Alyssa M Jespersen, Sundus Ahmed, Leonard P Wasieloski, Jeff Garrison, David A Kulesh, Ernst E Brueggemann, Tara Kenny, Michael D Ward, David E Harbourt, Timothy D Minogue
Research involving biosafety level 3 pathogens such as West Nile virus (WNV) is often limited by the limited space and technical constraints of these environments. To conduct complex analytical studies outside of high containment, robust and reliable inactivation methods are needed that maintain compatibility with downstream assays. Here we report the inactivation of WNV in spiked serum samples using a commercially available SDS-PAGE sample buffer for proteomic studies. Using this method, we demonstrate its utility by identification proteins differentially expressed in the serum of mice experimentally infected with WNV...
May 19, 2017: Journal of Virological Methods
https://www.readbyqxmd.com/read/28531865/glutamine-antagonist-mediated-immune-suppression-decreases-pathology-but-delays-virus-clearance-in-mice-during-nonfatal-alphavirus-encephalomyelitis
#17
Victoria K Baxter, Rebecca Glowinski, Alicia M Braxton, Michelle C Potter, Barbara S Slusher, Diane E Griffin
Infection of weanling C57BL/6 mice with the TE strain of Sindbis virus (SINV) causes nonfatal encephalomyelitis associated with hippocampal-based memory impairment that is partially prevented by treatment with 6-diazo-5-oxo-l-norleucine (DON), a glutamine antagonist (Potter et al., J Neurovirol 21:159, 2015). To determine the mechanism(s) of protection, lymph node and central nervous system (CNS) tissues from SINV-infected mice treated daily for 1 week with low (0.3mg/kg) or high (0.6mg/kg) dose DON were examined...
May 19, 2017: Virology
https://www.readbyqxmd.com/read/28531291/a-novel-virus-vectored-respiratory-mucosal-vaccine-enhances-anti-tuberculosis-immunity-in-a-humanized-model-system
#18
Yushi Yao, Rocky Lai, Sam Afkhami, Siamak Haddadi, Anna Zganiacz, Fatemeh Vahedi, Ali A Ashkar, Charu Kaushic, Mangalakumari Jeyanathan, Zhou Xing
Background: The translation of pre-clinically promising novel tuberculosis (TB) vaccines to ultimate human applications has met with the challenge of lacking markedly improved animal models for vaccine testing with an immune system of human equivalent in its genetic diversity and level of susceptibility to TB. Methods: We have developed a humanized mice (Hu-mice) TB model system to investigate the clinical relevance of a novel virus-vectored (VV) TB vaccine administered via respiratory mucosal (RM) or parenteral route...
May 20, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28531130/comparative-safety-and-efficacy-profile-of-a-novel-oil-in-water-vaccine-adjuvant-comprising-vitamins-a-and-e-and-a-catechin-in-protective-anti-influenza-immunity
#19
Sapna Patel, Yasser Faraj, Debra K Duso, William W Reiley, Erik A Karlsson, Stacey Schultz-Cherry, Michael Vajdy
Non-replicating vaccines, such as those based on recombinant proteins, require adjuvants and delivery systems, which have thus far depended on mimicking pathogen danger signals and strong pro-inflammatory responses. In search of a safer and more efficacious alternative, we tested whether vaccinations with influenza recombinant hemagglutinin (HA) mixed with a novel vegetable oil in water emulsion adjuvant (Natural Immune-enhancing Delivery System, NIDS), based on the immune-enhancing synergy of vitamins A and E and a catechin, could protect against intra-nasal challenge with live influenza virus...
May 21, 2017: Nutrients
https://www.readbyqxmd.com/read/28530712/the-microrna-mir-31-inhibits-cd8-t-cell-function-in-chronic-viral-infection
#20
Howell F Moffett, Adam N R Cartwright, Hye-Jung Kim, Jernej Godec, Jason Pyrdol, Tarmo Äijö, Gustavo J Martinez, Anjana Rao, Jun Lu, Todd R Golub, Harvey Cantor, Arlene H Sharpe, Carl D Novina, Kai W Wucherpfennig
During infection, antigen-specific T cells undergo tightly regulated developmental transitions controlled by transcriptional and post-transcriptional regulation of gene expression. We found that the microRNA miR-31 was strongly induced by activation of the T cell antigen receptor (TCR) in a pathway involving calcium and activation of the transcription factor NFAT. During chronic infection with lymphocytic choriomeningitis virus (LCMV) clone 13, miR-31-deficent mice recovered from clinical disease, while wild-type mice continued to show signs of disease...
May 22, 2017: Nature Immunology
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