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https://www.readbyqxmd.com/read/28207419/both-genome-and-cytosol-dynamics-change-in-e-coli-challenged-with-sublethal-rifampicin
#1
Michal Wlodarski, Bianca Raciti, Jurij Kotar, Marco Cosentino Lagomarsino, Gillian M Fraser, Pietro Cicuta
While the action of many antimicrobial drugs is well understood at the molecular level, a systems-level physiological response to antibiotics remains largely unexplored. This work considers fluctuation dynamics of both the chromosome and cytosol in Escherichia coli, and their response to sublethal treatments of a clinically important antibiotic, rifampicin. We precisely quantify the changes in dynamics of chromosomal loci and cytosolic aggregates (a rheovirus nonstructural protein known as μNS-GFP), measuring short time-scale displacements across several hours of drug exposure...
February 16, 2017: Physical Biology
https://www.readbyqxmd.com/read/28202376/structural-features-of-zika-virus-non-structural-proteins-3-and-5-and-its-individual-domains-in-solution-as-well-as-insights-into-ns3-inhibition
#2
Wuan Geok Saw, Ankita Pan, Malathy Sony Subramanian Manimekalai, Gerhard Grüber
Zika virus (ZIKV) has emerged as a pathogen of major health concern. The virus relies on its non-structural protein 5 (NS5) including a methyl-transferase (MTase) and a RNA-dependent RNA polymerase (RdRp) for capping and synthesis of the viral RNA and the nonstructural protein 3 (NS3) with its protease and helicase domain for polyprotein possessing, unwinding dsRNA proceeding replication, and NTPase/RTPase activities. In this study we present for the first time insights into the overall structure of the entire French Polynesia ZIKV NS3 in solution...
February 12, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28198446/a-mutation-identified-in-neonatal-microcephaly-destabilizes-zika-virus-ns1-assembly-in-vitro
#3
Deping Wang, Cheng Chen, Shengnan Liu, Han Zhou, Kailin Yang, Qi Zhao, Xiaoyun Ji, Chen Chen, Wei Xie, Zefang Wang, Li-Zhi Mi, Haitao Yang
An unprecedented epidemic of Zika virus (ZIKV) infection had spread to South and Central America. ZIKV infection was recently confirmed by CDC (the Centers for Disease Control and Prevention) to cause neonatal microcephaly, which posed a significant public health emergency of international concern. No specific vaccines or drugs are currently available to fight ZIKV infection. ZIKV nonstructural protein 1 (NS1) plays an essential role in viral replication and immune evasion. We determined the crystal structure of ZIKV NS1172-352, which forms a head-to-head, symmetric dimer with a unique 14-stranded β-ladder conserved among flaviviruses...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28196962/spatial-and-temporal-analysis-of-alphavirus-replication-and-assembly-in-mammalian-and-mosquito-cells
#4
Joyce Jose, Aaron B Taylor, Richard J Kuhn
Sindbis virus (SINV [genus Alphavirus, family Togaviridae]) is an enveloped, mosquito-borne virus. Alphaviruses cause cytolytic infections in mammalian cells while establishing noncytopathic, persistent infections in mosquito cells. Mosquito vector adaptation of alphaviruses is a major factor in the transmission of epidemic strains of alphaviruses. Though extensive studies have been performed on infected mammalian cells, the morphological and structural elements of alphavirus replication and assembly remain poorly understood in mosquito cells...
February 14, 2017: MBio
https://www.readbyqxmd.com/read/28193518/safety-and-efficacy-of-elbasvir-grazoprevir-in-patients-with-hepatitis-c-virus-infection-and-compensated-cirrhosis-an-integrated-analysis
#5
Ira M Jacobson, Eric Lawitz, Paul Y Kwo, Christophe Hézode, Cheng-Yuan Peng, Anita Y M Howe, Peggy Hwang, Janice Wahl, Michael Robertson, Eliav Barr, Barbara A Haber
BACKGROUND & AIMS: Persons with hepatitis C virus (HCV) infection are at risk of progressive liver disease, cirrhosis, and decompensation. We analyzed the effects of the direct-acting antiviral agents elbasvir and grazoprevir in patients with HCV infection and compensated cirrhosis, combining data from 6 clinical trials. METHODS: We performed an integrated analysis of 402 patients with HCV genotype 1, 4, or 6 infection and Child-Pugh A compensated cirrhosis enrolled in 6 clinical trials...
February 10, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28175982/complete-genome-sequence-of-menghai-flavivirus-a-novel-insect-specific-flavivirus-from-china
#6
Xianglilan Zhang, Xiaofang Guo, Hang Fan, Qiumin Zhao, Shuqing Zuo, Qiang Sun, Guangqian Pei, Shi Cheng, Xiaoping An, Yunfei Wang, Zhiqiang Mi, Yong Huang, Zhiyi Zhang, Yigang Tong, Hongning Zhou, Jiusong Zhang
Menghai flavivirus (MFV) was isolated from Aedes albopictus in Menghai county of Yunnan Province, China, during an arboviruses screening program in August 2010. Whole genome sequencing of MFV was performed using an Ion PGM™ Sequencer. The complete genome of MFV was 10897 nucleotides in length and encoded a polyprotein and fairly interesting flavivirus orf (FIFO). The polyprotein contained three flavivirus structural proteins (C, prM/M and E) and seven nonstructural proteins. Nucleotide BLAST analysis revealed that the MFV genome showed highest similarity to Xishuangbanna Aedes flavivirus, a novel insect-specific flavivirus recently isolated from the same area...
February 7, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28164628/evaluation-of-truncated-hcv-ns3-protein-for-potential-applications-in-immunization-and-diagnosis
#7
Foozieh Javadi, Pooneh Rahimi, Mohammad Hossien Modarressi, Azam Bolhassani, Mehdi Shafiee Ardestani, Seyed Mehdi Sadat, Mohammad Reza Aghasadeghi
BACKGROUND: Hepatitis C virus infection is one of global health concern. No vaccine is available so far and nonstructural protein 3 (NS3) is one of the main target antigens for developing studies on therapeutic vaccine and diagnostic application. In the current study, we expressed a truncated recombinant HCV-NS3 protein under native condition and evaluated its potential applications in immunization and diagnosis. METHODS: The recombinant pET-NS3 containing a truncated form of HCV NS3 region was constructed, confirmed by sequencing reactions, and expressed into E...
July 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28159444/detection-and-differentiation-of-norovirus-genogroups-i-and-ii-from-clinical-stool-specimens-using-real-time-pcr
#8
Poornima Ramanan, M J Espy, Reeti Khare, M J Binnicker
A real-time RT-PCR assay was designed to detect and differentiate norovirus genogroups I (GI) and II (GII), with primers and probes targeting the nonstructural polyprotein gene. Stool samples (n = 100) submitted for routine testing by the BioFire FilmArray® GI panel were also tested by the norovirus GI/GII real-time PCR assays. When compared to the FilmArray GI panel, the norovirus real-time PCR assay demonstrated a sensitivity of 77.5% (62/80) and specificity of 95% (19/20). Specimens yielding discordant results (n = 19) were tested at two outside laboratories for adjudication...
January 20, 2017: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/28151973/a-positive-strand-rna-virus-uses-alternative-protein-protein-interactions-within-a-viral-protease-cofactor-complex-to-switch-between-rna-replication-and-virion-morphogenesis
#9
Danilo Dubrau, M Alejandra Tortorici, Félix A Rey, Norbert Tautz
The viruses of the family Flaviviridae possess a positive-strand RNA genome and express a single polyprotein which is processed into functional proteins. Initially, the nonstructural (NS) proteins, which are not part of the virions, form complexes capable of genome replication. Later on, the NS proteins also play a critical role in virion formation. The molecular basis to understand how the same proteins form different complexes required in both processes is so far unknown. For pestiviruses, uncleaved NS2-3 is essential for virion morphogenesis while NS3 is required for RNA replication but is not functional in viral assembly...
February 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28148797/patterns-of-cellular-immunity-associated-with-experimental-infection-with-rden2%C3%AE-30-tonga-74-supports-its-suitability-as-a-human-denv-challenge-strain
#10
Alba Grifoni, Michael Angelo, John Sidney, Sinu Paul, Bjoern Peters, Aruna D de Silva, Elizabeth Phillips, Simon Mallal, Sean A Diehl, Jason Botten, Jonathan Boyson, Beth D Kirkpatrick, Stephen S Whitehead, Anna P Durbin, Alessandro Sette, Daniela Weiskopf
: A deletion variant of the DENV2 Tonga/74 strain lacking 30 nucleotides from its 3' untranslated region (rDEN2Δ30) has previously been established for use in a controlled DENV human challenge model. To evaluate if this model is appropriate to derive correlates of protection for DENV vaccines based on cellular immunity, we wanted to compare how the cellular immune response to this challenge strain compares to the response induced by natural infection. To achieve this, we predicted HLA class I and class II restricted peptides from rDEN2Δ30 and used them, in an IFN-gamma ELISPOT assay, to interrogate CD8(+) and CD4(+) T cell responses in healthy volunteers infected with rDEN2Δ30...
February 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28143984/in-situ-tagged-nsp15-reveals-interactions-with-coronavirus-replication-transcription-complex-associated-proteins
#11
Jeremiah Athmer, Anthony R Fehr, Matthew Grunewald, Everett Clinton Smith, Mark R Denison, Stanley Perlman
: Coronavirus (CoV) replication and transcription are carried out in close proximity to restructured endoplasmic reticulum (ER) membranes in replication/transcription complexes (RTC). Many of the CoV nonstructural proteins (nsps) are required for RTC function; however, not all of their functions are known. nsp15 contains an endoribonuclease domain that is conserved in the CoV family. While the enzymatic activity and crystal structure of nsp15 are well defined, its role in replication remains elusive...
January 31, 2017: MBio
https://www.readbyqxmd.com/read/28143925/adp-ribosylhydrolase-activity-of-chikungunya-virus-macrodomain-is-critical-for-virus-replication-and-virulence
#12
Robert Lyle McPherson, Rachy Abraham, Easwaran Sreekumar, Shao-En Ong, Shang-Jung Cheng, Victoria K Baxter, Hans A V Kistemaker, Dmitri V Filippov, Diane E Griffin, Anthony K L Leung
Chikungunya virus (CHIKV), an Old World alphavirus, is transmitted to humans by infected mosquitoes and causes acute rash and arthritis, occasionally complicated by neurologic disease and chronic arthritis. One determinant of alphavirus virulence is nonstructural protein 3 (nsP3) that contains a highly conserved MacroD-type macrodomain at the N terminus, but the roles of nsP3 and the macrodomain in virulence have not been defined. Macrodomain is a conserved protein fold found in several plus-strand RNA viruses that binds to the small molecule ADP-ribose...
January 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28142057/the-effect-of-classical-swine-fever-virus-ns5a-and-ns5a-mutants-on-oxidative-stress-and-inflammatory-response-in-swine-testicular-cells
#13
Wang Dong, Huifang Lv, Yifan Wang, Xiaomeng Li, Cheng Li, Lu Wang, Chengbao Wang, Kangkang Guo, Yanming Zhang
Infection with classical swine fever virus (CSFV) results in highly significant economic losses; this infection is characterized by being highly contagious and accompanied by hyperthermia and systemic bleeding. Oxidative stress (OS) plays a critical role in the pathological process of viral infection. The function of the nonstructural protein 5A (NS5A) in the pathogenesis of CSFV has not been completely understood. Here, OS and the inflammatory response were studied with NS5A and substitution mutants in swine testicular (ST) cells...
January 13, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28137864/entirely-plasmid-based-reverse-genetics-system-for-rotaviruses
#14
Yuta Kanai, Satoshi Komoto, Takahiro Kawagishi, Ryotaro Nouda, Naoko Nagasawa, Misa Onishi, Yoshiharu Matsuura, Koki Taniguchi, Takeshi Kobayashi
Rotaviruses (RVs) are highly important pathogens that cause severe diarrhea among infants and young children worldwide. The understanding of the molecular mechanisms underlying RV replication and pathogenesis has been hampered by the lack of an entirely plasmid-based reverse genetics system. In this study, we describe the recovery of recombinant RVs entirely from cloned cDNAs. The strategy requires coexpression of a small transmembrane protein that accelerates cell-to-cell fusion and vaccinia virus capping enzyme...
January 30, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28131854/a-structural-view-of-the-rna-dependent-rna-polymerases-from-the-flavivirus-genus
#15
REVIEW
Guoliang Lu, Peng Gong
The RNA-dependent RNA polymerase (RdRP) from the Flavivirus genus is naturally fused to a methyltransferase (MTase), and the full-length protein is named nonstructural protein 5 (NS5). Similar to polymerases from other RNA viruses, the flavivirus RdRP has an encircled human right hand architecture with palm, fingers, and thumb domains surrounding its polymerase active site. In contrast to primer-dependent RdRPs that have a spacious front channel to accommodate the template-product RNA duplex, the flavivirus RdRP has a priming element as a thumb domain insertion, partially occupying the front channel to facilitate the de novo initiation process...
January 25, 2017: Virus Research
https://www.readbyqxmd.com/read/28125002/feline-panleucopenia-virus-ns2-suppresses-the-host-ifn-%C3%AE-induction-by-disrupting-the-interaction-between-tbk1-and-sting
#16
Hongtao Kang, Dafei Liu, Jin Tian, Xiaoliang Hu, Xiaozhan Zhang, Hang Yin, Hongxia Wu, Chunguo Liu, Dongchun Guo, Zhijie Li, Qian Jiang, Jiasen Liu, Liandong Qu
Feline panleucopenia virus (FPV) is a highly infectious pathogen that causes severe diseases in pets, economically important animals and wildlife in China. Although FPV was identified several years ago, little is known about how it overcomes the host innate immunity. In the present study, we demonstrated that infection with the FPV strain Philips-Roxane failed to activate the interferon β (IFN-β) pathway but could antagonize the induction of IFN stimulated by Sendai virus (SeV) in F81 cells. Subsequently, by screening FPV nonstructural and structural proteins, we found that only nonstructural protein 2 (NS2) significantly suppressed IFN expression...
January 23, 2017: Viruses
https://www.readbyqxmd.com/read/28122984/parvovirus-expresses-a-small-noncoding-rna-that-plays-an-essential-role-in-virus-replication
#17
Zekun Wang, Weiran Shen, Fang Cheng, Xuefeng Deng, John F Engelhardt, Ziying Yan, Jianming Qiu
: Human bocavirus 1 (HBoV1) belongs to species Primate bocaparvovirus of the genus Bocaparvovirus of the Parvoviridae family. HBoV1 causes acute respiratory tract infections in young children and has a selective tropism for the apical surface of well-differentiated human airway epithelia (HAE). In this study, we identify an additional HBoV1 gene, bocavirus-transcribed small non-coding RNA (BocaSR) within the 3' non-coding region (nt 5199-5338) of the viral genome of positive sense. BocaSR is transcribed by RNA polymerase III (Pol III) from an intragenic promoter at similar levels to that of the capsid protein-coding mRNA and is essential for replication of the viral DNA in both transfected HEK293 and infected HAE cells...
January 25, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28122329/the-conformational-changes-of-zika-virus-methyltransferase-upon-converting-sam-to-sah
#18
Han Zhou, Fenghua Wang, Haofeng Wang, Cheng Chen, Tianqing Zhang, Xu Han, Deping Wang, Chen Chen, Chen Wu, Wei Xie, Zefang Wang, Lei Zhang, Lanfeng Wang, Haitao Yang
An outbreak of Zika virus (ZIKV) infection has been reported in South and Central America and the Caribbean. Neonatal microcephaly potentially associated with ZIKV infection has already caused a public health emergency of international concern. Currently, there are no clinically effective vaccines or antiviral drugs available to treat ZIKV infection. The methyltransferase domain (MTase) of ZIKV nonstructural protein 5 (NS5) can sequentially methylate guanine N-7 and ribose 2'-O to form m7NGpppA2'Om cap structure in the new RNA transcripts...
January 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28120180/a-truncated-apoptin-protein-variant-selectively-kills-cancer-cells
#19
Santiago Ruiz-Martínez, Jessica Castro, Maria Vilanova, Marta Bruix, Douglas V Laurents, Marc Ribó, Antoni Benito
Apoptin is a nonstructural protein encoded by one of the three open reading frames of the chicken anemia virus genome. It has attracted a great deal of interest due to its ability to induce apoptosis in multiple transformed and malignant mammalian cell lines without affecting primary and non-transformed cells. However, the use of Apoptin as an anticancer drug is restricted by its strong tendency to aggregate. A number of methods to overcome this problem have been proposed, including transduction techniques to deliver the Apoptin gene into tumor cells, but all such methods have certain drawbacks...
January 24, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28112593/oral-combination-vaccine-comprising-bifidobacterium-displaying-hepatitis-c-virus-nonstructural-protein-3-and-interferon-%C3%AE-induces-strong-cellular-immunity-specific-to-nonstructural-protein-3-in-mice
#20
Koichi Kitagawa, Chika Omoto, Tsugumi Oda, Ayame Araki, Hiroki Saito, Katsumi Shigemura, Takane Katayama, Hak Hotta, Toshiro Shirakawa
We previously generated an oral hepatitis C virus (HCV) vaccine using Bifidobacterium displaying the HCV nonstructural protein 3 (NS3) polypeptide. NS3-specific cellular immunity is important for viral clearance and recovery from HCV infection. In this study, we enhanced the cellular immune responses induced by our oral HCV vaccine, Bifidobacterium longum 2165 (B. longum 2165), by combining interferon-α (IFN-α) as an adjuvant with the vaccine in a mouse experimental model. IFN-α is a widely used cytokine meeting the standard of care (SOC) for HCV infection and plays various immunoregulatory roles...
January 23, 2017: Viral Immunology
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