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https://www.readbyqxmd.com/read/28095684/effect-of-the-protein-corona-on-antibody-antigen-binding-in-nanoparticle-sandwich-immunoassays
#1
Helena de Puig, Irene Bosch, Marc Carré-Camps, Kimberly Hamad-Schifferli
We investigated the effect of the protein corona on the function of nanoparticle (NP) antibody (Ab) conjugates in dipstick sandwich immunoassays. Ab specific for Zika virus nonstructural protein 1 (NS1) were conjugated to gold NPs, and another anti-NS1 Ab was immobilized onto the nitrocellulose membrane. Sandwich immunoassay formation was influenced by whether the strip was run in corona forming conditions, i.e., in human serum. Strips run in buffer or pure solutions of bovine serum albumin exhibited false positives, but those run in human serum did not...
January 18, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28094237/a-multiplex-microsphere-immunoassay-for-zika-virus-diagnosis
#2
Susan J Wong, Andrea Furuya, Jing Zou, Xuping Xie, Alan P Dupuis, Laura D Kramer, Pei-Yong Shi
Rapid and accurate diagnosis of infectious agents is essential for patient care, disease control, and countermeasure development. The present serologic diagnosis of Zika virus (ZIKV) infection relies mainly on IgM-capture ELISA which is confounded with the flaw of cross-reactivity among different flaviviruses. In this communication, we report a multiplex microsphere immunoassay (MIA) that captures the diagnostic power of viral envelope protein (that elicits robust, yet cross-reactive antibodies to other flaviviruses) and the differential power of viral nonstructural proteins NS1 and NS5 (that induce more virus-type specific antibodies)...
January 10, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28077630/mavs-is-essential-for-primary-cd4-t-cell-immunity-but-not-for-recall-t-cell-responses-following-an-attenuated-west-nile-virus-infection
#3
Huanle Luo, Evandro Winkelmann, Guorui Xie, Rong Fang, Bi-Hung Peng, Li Li, Helen M Lazear, Slobodan Paessler, Michael S Diamond, Michael Gale, Alan D Barrett, Tian Wang
: The use of pathogen recognition receptor (PRR) agonists and the molecular mechanisms involved have been the major focus of research in individual vaccine development. West Nile virus (WNV) nonstructural (NS) 4B-P38G mutant has several features for an ideal vaccine candidate, including significantly reduced neuroinvasiveness, induction of strong adaptive immunity, and protection of mice from wild-type (WT) WNV infection. Here, we determined the role of mitochondrial antiviral-signaling (MAVS), the adaptor protein for RIG-I like receptor in regulating host immunity against the NS4B-P38G vaccine...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28067309/the-autophagy-elongation-complex-atg5-12-16l1-positively-regulates-hcv-replication-and-is-required-for-wild-type-membranous-web-formation
#4
Ahmed M Fahmy, Patrick Labonté
Hepatitis C virus (HCV) infection induces intracellular membrane rearrangements, thus forming a membranous web (MW) in which HCV replication and assembly occur. The HCV-induced MW is primarily composed of double membrane vesicles (DMVs) transfused by multi-membrane vesicles. The autophagy machinery has been proposed to participate in the formation of such vesicles. However, no clear evidence has been found linking autophagy to the formation of these DMVs. In this study, we evaluated the role of the autophagy elongation complex (ATG5-12/16L1) in HCV replication and MW formation...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28053107/domain-organization-and-evolution-of-the-highly-divergent-5-coding-region-of-genomes-of-arteriviruses-including-the-novel-possum-nidovirus
#5
Anastasia Gulyaeva, Magdalena Dunowska, Erik Hoogendoorn, Julia Giles, Dmitry Samborskiy, Alexander E Gorbalenya
: In five experimentally characterized arterivirus species, the 5' -end genome coding region comprises most divergent nonstructural proteins (nsp) 1 and 2 that include papain-like proteases (PLPs) and other poorly characterized domains. They are involved in regulation of transcription, polyprotein processing, and virus-host interaction. Here, we present results of bioinformatics analysis of this region of 14 arterivirus species, including that of the most distantly related wobbly possum disease virus (WPDV), determined by a modified 5' RACE protocol...
January 4, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28049830/characterization-of-cytopathic-factors-through-genome-wide-analysis-of-the-zika-viral-proteins-in-fission-yeast
#6
Ge Li, Melissa Poulsen, Csaba Fenyvuesvolgyi, Yoko Yashiroda, Minoru Yoshida, J Marc Simard, Robert C Gallo, Richard Y Zhao
The Zika virus (ZIKV) causes microcephaly and the Guillain-Barré syndrome. Little is known about how ZIKV causes these conditions or which ZIKV viral protein(s) is responsible for the associated ZIKV-induced cytopathic effects, including cell hypertrophy, growth restriction, cell-cycle dysregulation, and cell death. We used fission yeast for the rapid, global functional analysis of the ZIKV genome. All 14 proteins or small peptides were produced under an inducible promoter, and we measured the intracellular localization and the specific effects on ZIKV-associated cytopathic activities of each protein...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28044043/adaptive-diversification-between-yellow-fever-virus-west-african-and-south-american-lineages-a-genome-wide-study
#7
Yan Li, Zexiao Yang
Yellow fever virus (YFV) has emerged as the causative agent of a vector-borne disease with devastating mortality in the tropics of Africa and the Americas. YFV phylogenies indicate that the isolates collected from West Africa, East and Central Africa, and South America cluster into different lineages and the virus spread into the Americas from Africa. To determine the nature of genetic variation accompanying the intercontinental epidemic, we performed a genome-wide evolutionary study on the West African and South American lineages of YFV...
January 2, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28035485/action-and-function-of-wnt-%C3%AE-catenin-signaling-in-the-progression-from-chronic-hepatitis-c-to-hepatocellular-carcinoma
#8
REVIEW
Wenhui Wang, Qiuwei Pan, Gwenny M Fuhler, Ron Smits, Maikel P Peppelenbosch
Hepatitis C virus (HCV) infection is one of the leading causes of hepatocellular carcinoma (HCC) worldwide but the mechanistic basis as to how chronic HCV infection furthers the HCC process remains only poorly understood. Accumulating evidence indicates that HCV core and nonstructural proteins provoke activation of the Wnt/β-catenin signaling pathway, and the evidence supporting a role of Wnt/β-catenin signaling in the onset and progression of HCC is compelling. Convincing molecular explanations as to how expression of viral effectors translates into increased activity of the Wnt/β-catenin signaling machinery are still largely lacking, hampering the design of rational strategies aimed at preventing HCC...
December 29, 2016: Journal of Gastroenterology
https://www.readbyqxmd.com/read/28034779/a-mitochondrial-membrane-protein-is-a-target-for-rice-ragged-stunt-virus-in-its-insect-vector
#9
Hai-Jian Huang, Cheng-Wen Liu, Xiang Zhou, Chuan-Xi Zhang, Yan-Yuan Bao
Rice ragged stunt virus (RRSV; Reoviridae) is exclusively transmitted by the brown planthopper Nilaparvata lugens in a persistent-propagative manner. It is understood that RNA viral proliferation is associated with the intracellular membranes of the insect host cells. However, the molecular mechanisms of the interaction between the RRSV proliferation and the intracellular membranes remain essentially unknown. It will be of great interest to determine whether RRSV protein(s) directly interact with intracellular membrane components of its host cells...
February 2, 2017: Virus Research
https://www.readbyqxmd.com/read/28034492/addition-of-ribavirin-to-daclatasvir-plus-asunaprevir-for-chronic-hepatitis-c-1b-patients-with-baseline-ns5a-resistance-associated-variants-improved-response
#10
Chun-Ming Hong, Chun-Jen Liu, Shiou-Hwei Yeh, Pei-Jer Chen
BACKGROUND/PURPOSE: Daclatasvir is a nonstructural protein 5A inhibitor with potent activity against hepatitis C virus genotypes 1-6 in vitro, and asunaprevir is a nonstructural protein 3 protease inhibitor with activity against genotypes 1, 4, 5, and 6. Despite a 90% sustained virologic response (SVR) rate, the SVR rate in patients with baseline NS5A-L31/Y93H polymorphisms decreased to around 40%. Therefore, an alternative regimen under the consideration of cost-effectiveness would be important...
December 26, 2016: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/28003482/ns1-protein-amino-acid-changes-d189n-and-v194i-affect-interferon-responses-thermosensitivity-and-virulence-of-circulating-h3n2-human-influenza-a-viruses
#11
Aitor Nogales, Luis Martinez-Sobrido, David J Topham, Marta L DeDiego
: Influenza NS1 protein is a non-structural, multifunctional protein that counteracts host innate immune responses, modulating virus pathogenesis. NS1 protein variability in subjects infected with H3N2 IAVs during the 2010/2011 season was analyzed, finding amino acid changes in residues 86, 189, and 194. The consequences of these mutations in the NS1-mediated inhibition of IFN responses, and the pathogenesis of the virus were evaluated, showing that NS1 mutations D189N, and V194I impaired the ability of the NS1 protein to inhibit general gene expression, most probably because these mutations decreased the binding of NS1 to the cleavage and polyadenylation specificity factor 30 (CPSF30)...
December 21, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27998085/structural-insight-into-ns5-of-zika-virus-leading-to-the-discovery-of-mtase-inhibitors
#12
Preyesh Stephen, Mariana Baz, Guy Boivin, Sheng-Xiang Lin
Zika virus (ZIKV) is an emerging mosquito-borne virus recently linked to intrauterine growth restriction including abnormal fetal brain development. The recent outbreak of ZIKV reached pandemic level resulting in an alarming public health emergency. At present, there is limited understanding of the infectious mechanism and no approved therapy. Nonstructural protein 5 is essential for capping and replication of viral RNA and comprises a methyltransferase (MTase) and RNA dependent RNA polymerase domain. Here we used molecular modeling to obtain the structure of ZIKV MTase and molecular docking to identify the additional hydrophobic region uniquely conserved in flavivirus MTase that can be used as a druggable site...
December 21, 2016: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/27997564/nonstructural-protein-11-of-porcine-reproductive-and-respiratory-syndrome-virus-suppresses-both-mavs-and-rig-i-expression-as-one-of-the-mechanisms-to-antagonize-type-i-interferon-production
#13
Yan Sun, Hanzhong Ke, Mingyuan Han, Ning Chen, Weihuan Fang, Dongwan Yoo
Type I interferons (IFN-α/β) play a key role in antiviral defense, and porcine reproductive and respiratory syndrome virus (PRRSV) is known to down-regulate the IFN response in virus-infected cells and pigs. In this study, we showed that the overexpression of nsp11 of PRRSV induced a strong suppression of IFN production. Nsp11 suppressed both IRF3 and NF-κB activities when stimulated with a dsRNA analogue and TNF-α, respectively. This suppression was RLR dependent, since the transcripts and proteins of MAVS and RIG-I, two critical factors in RLR-mediated pathway, were both found to be reduced in the presence of overexpressed nsp11...
2016: PloS One
https://www.readbyqxmd.com/read/27986564/inhibition-of-japanese-encephalitis-virus-jev-replication-by-specific-rna-aptamer-against-jev-methyltransferase
#14
Seung Ryul Han, Seong-Wook Lee
Japanese encephalitis virus (JEV) is the most common etiological agent of epidemic viral encephalitis. JEV encodes a single methyltransferase (MTase) domain located at the N-terminal region of the viral nonstructural protein NS5. JEV MTase is essential for viral replication and specifically catalyzes methylation of the viral RNA cap, which occurs exclusively in the cytoplasm. Therefore, JEV MTase is a potential target for antiviral therapy. Here, we identified specific and avid RNA aptamer (Kd ∼ 12 nM) with modified 2'-O-methyl pyrimidines against JEV MTase...
December 13, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27984784/porcine-deltacoronavirus-nsp5-inhibits-interferon-%C3%AE-production-through-the-cleavage-of-nemo
#15
Xinyu Zhu, Liurong Fang, Dang Wang, Yuting Yang, Jiyao Chen, Xu Ye, Mohamed Frahat Foda, Shaobo Xiao
Porcine deltacoronavirus (PDCoV) causes acute enteric disease and mortality in seronegative neonatal piglets. Previously we have demonstrated that PDCoV infection suppresses the production of interferon-beta (IFN-β), while the detailed mechanisms are poorly understood. Here, we demonstrate that nonstructural protein 5 (nsp5) of PDCoV, the 3C-like protease, significantly inhibits Sendai virus (SEV)-induced IFN-β production by targeting the NF-κB essential modulator (NEMO), confirmed by the diminished function of NEMO cleaved by PDCoV...
December 13, 2016: Virology
https://www.readbyqxmd.com/read/27984114/glutathionylation-of-chikungunya-nsp2-protein-affects-protease-activity
#16
Chonticha Saisawang, Atichat Kuadkitkan, Duncan R Smith, Sukathida Ubol, Albert J Ketterman
BACKGROUND: Chikungunya fever is an emerging disease caused by the chikungunya virus and is now being spread worldwide by the mosquito Aedes albopictus. The infection can cause a persistent severe joint pain and recent reports link high levels of viremia to neuropathologies and fatalities. The viral protein nsP2 is a multifunctional enzyme that plays several critical roles in virus replication. Virus infection induces oxidative stress in host cells which the virus utilizes to aid viral propagation...
February 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27965448/the-conserved-coronavirus-macrodomain-promotes-virulence-and-suppresses-the-innate-immune-response-during-severe-acute-respiratory-syndrome-coronavirus-infection
#17
Anthony R Fehr, Rudragouda Channappanavar, Gytis Jankevicius, Craig Fett, Jincun Zhao, Jeremiah Athmer, David K Meyerholz, Ivan Ahel, Stanley Perlman
: ADP-ribosylation is a common posttranslational modification that may have antiviral properties and impact innate immunity. To regulate this activity, macrodomain proteins enzymatically remove covalently attached ADP-ribose from protein targets. All members of the Coronavirinae, a subfamily of positive-sense RNA viruses, contain a highly conserved macrodomain within nonstructural protein 3 (nsp3). However, its function or targets during infection remain unknown. We identified several macrodomain mutations that greatly reduced nsp3's de-ADP-ribosylation activity in vitro Next, we created recombinant severe acute respiratory syndrome coronavirus (SARS-CoV) strains with these mutations...
December 13, 2016: MBio
https://www.readbyqxmd.com/read/27957384/mitigating-the-risk-of-transfusion-transmitted-dengue-in-australia
#18
Kelly Rooks, Clive R Seed, Jesse J Fryk, Catherine A Hyland, Robert J Harley, Jerry A Holmberg, Denese C Marks, Robert L P Flower, Helen M Faddy
Dengue viruses (DENV 1-4) are a risk to transfusion safety, with several transfusion-transmitted (TT) cases reported globally. DENV 1-4 are endemic in over 100 countries, with seasonal outbreaks occurring in northeastern Australia. To mitigate TT-DENV risk in Australia, fresh blood components are not manufactured from donors returning from any area (domestic/overseas) with known dengue transmission. Alternatively, TT-DENV risk may be mitigated using an appropriate blood donor screening assay. We aimed to determine the rate of dengue infection in donors during dengue outbreaks in Australia...
2016: Journal of Blood Transfusion
https://www.readbyqxmd.com/read/27925288/genomic-sequence-and-virulence-evaluation-of-mn184a-like-porcine-reproductive-and-respiratory-syndrome-virus-in-japan
#19
Hiroshi Iseki, Takeya Morozumi, Michihiro Takagi, Kenji Kawashima, Tomoyuki Shibahara, Hirohide Uenishi, Hiroshi Tsunemitsu
This study characterized a porcine reproductive and respiratory syndrome virus (PRRSV) that was isolated in Japan from a 9-week-old diseased pig on a farm with an increased mortality rate during 2007-2008. This unique isolate, designated as Jpn5-37, did not have a high nucleotide identity in open reading frame 5 against any Japanese isolates. Among all available type 2 PRRSV complete genome sequences, Jpn5-37 shared the highest nucleotide identity (93.6%) with virulent strain MN184A. The genomic characteristics of Jpn5-37 were highly conserved with respect to the virulent MN184A, including a continuous 8-amino acid deletion in the nonstructural protein 2 region...
December 7, 2016: Microbiology and Immunology
https://www.readbyqxmd.com/read/27923923/antiviral-innate-immune-response-interferes-with-the-formation-of-replication-associated-membrane-structures-induced-by-a-positive-strand-rna-virus
#20
Diede Oudshoorn, Barbara van der Hoeven, Ronald W A L Limpens, Corrine Beugeling, Eric J Snijder, Montserrat Bárcena, Marjolein Kikkert
: Infection with nidoviruses like corona- and arteriviruses induces a reticulovesicular network of interconnected endoplasmic reticulum (ER)-derived double-membrane vesicles (DMVs) and other membrane structures. This network is thought to accommodate the viral replication machinery and protect it from innate immune detection. We hypothesized that the innate immune response has tools to counteract the formation of these virus-induced replication organelles in order to inhibit virus replication...
December 6, 2016: MBio
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