Host Cell & Pathogen Interactions
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Processing of the Ebola virus glycoprotein by the proprotein convertase furin

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In the present study, we have investigated processing and maturation of the envelope glycoprotein (GP) of Ebola virus. When GP expressed from vaccinia virus vectors was analyzed by pulse–chase experiments, the mature form and two different precursors were identified. First, the endoplasmic reticulum form preGPer, full-length GP with oligomannosidic N-glycans, was detected. preGPer (110 kDa) was replaced by the Golgi-specific form preGP (160 kDa), full-length GP containing mature carbohydrates. preGP was finally converted by proteolysis into mature GP1,2, which consisted of two disulfide-linked cleavage products, the amino-terminal 140-kDa fragment GP1, and the carboxyl-terminal 26-kDa fragment GP2. GP1,2 was also identified in Ebola virions. Studies employing site-directed mutagenesis revealed that GP was cleaved at a multibasic amino acid motif located at positions 497 to 501 of the ORF. Cleavage was blocked by a peptidyl chloromethylketone containing such a motif. GP is cleaved by the proprotein convertase furin. This was indicated by the observation that cleavage did not occur when GP was expressed in furin-defective LoVo cells but that it was restored in these cells by vector-expressed furin. The Reston subtype, which differs from all other Ebola viruses by its low human pathogenicity, has a reduced cleavability due to a mutation at the cleavage site. As a result of these observations, it should now be considered that proteolytic processing of GP may be an important determinant for the pathogenicity of Ebola virus.

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Kenzibit's curator insight, August 3, 2014 2:50 PM

In the present study, we have investigated processing and maturation of the envelope glycoprotein (GP) of Ebola virus. When GP expressed from vaccinia virus vectors was analyzed by pulse–chase experiments, the mature form and two different precursors were identified. First, the endoplasmic reticulum form preGPer, full-length GP with oligomannosidic N-glycans, was detected. preGPer (110 kDa) was replaced by the Golgi-specific form preGP (160 kDa), full-length GP containing mature carbohydrates. preGP was finally converted by proteolysis into mature GP1,2, which consisted of two disulfide-linked cleavage products, the amino-terminal 140-kDa fragment GP1, and the carboxyl-terminal 26-kDa fragment GP2. GP1,2 was also identified in Ebola virions. Studies employing site-directed mutagenesis revealed that GP was cleaved at a multibasic amino acid motif located at positions 497 to 501 of the ORF. Cleavage was blocked by a peptidyl chloromethylketone containing such a motif. GP is cleaved by the proprotein convertase furin. This was indicated by the observation that cleavage did not occur when GP was expressed in furin-defective LoVo cells but that it was restored in these cells by vector-expressed furin. The Reston subtype, which differs from all other Ebola viruses by its low human pathogenicity, has a reduced cleavability due to a mutation at the cleavage site. As a result of these observations, it should now be considered that proteolytic processing of GP may be an important determinant for the pathogenicity of Ebola virus.

Host Cell & Pathogen Interactions
Strategies of Microbial Virulence and Host Defense
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Scientists enhance ability of antibiotics to defeat resistant types of bacteria using molecules called PPMOs - Scienmag

Scientists enhance ability of antibiotics to defeat resistant types of bacteria using molecules called PPMOs - Scienmag | Host Cell & Pathogen Interactions | Scoop.it
UT Southwestern researchers (l-r) Dr. Erdal Toprak, Dr. Seth Daly, Yusuf Talha Tamer, and Dr. David Greenberg reported successful use of a synthetic molecule to enhance antibiotic effectiveness agains..
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Duke University sued for fabricating research data to win millions in federal grants

Duke University sued for fabricating research data to win millions in federal grants | Host Cell & Pathogen Interactions | Scoop.it
A former researcher from Duke University has filed a lawsuit against the school, claiming fellow researchers fabricated data to win millions of dollars in federal grants.
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Cellular & Molecular Immunology - Outrunning the Red Queen: bystander activation as a means of outpacing innate immune subversion by intracellular pathogens

Cellular & Molecular Immunology - Outrunning the Red Queen: bystander activation as a means of outpacing innate immune subversion by intracellular pathogens | Host Cell & Pathogen Interactions | Scoop.it
Cellular and Molecular Immunology aims to report the dynamic progress being made in China and abroad in immunological research, and welcomes high-quality Research Articles, Reviews and Brief Reports across a broad range of topics including, but not...
Via Gilbert C FAURE
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Gilbert C FAURE's curator insight, August 25, 3:51 AM
the red queen and Alice
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Fc receptors in antibody-dependent enhancement of viral infections - Taylor - 2015 - Immunological Reviews - Wiley Online Library

Fc receptors in antibody-dependent enhancement of viral infections - Taylor - 2015 - Immunological Reviews - Wiley Online Library | Host Cell & Pathogen Interactions | Scoop.it

Via Gilbert C FAURE
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Maternal HIV status may disrupt normal microbiome development in uninfected infants

Maternal HIV status may disrupt normal microbiome development in uninfected infants | Host Cell & Pathogen Interactions | Scoop.it
A study led by researchers at The Saban Research Institute of Children's Hospital Los Angeles (CHLA) suggests that maternal HIV infection influences the microbiome of their HIV-uninfected infants. Their findings, reporte
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Complement in disease: a defence system turning offensive : Nature Reviews Nephrology : Nature Publishing Group

Complement in disease: a defence system turning offensive : Nature Reviews Nephrology : Nature Publishing Group | Host Cell & Pathogen Interactions | Scoop.it
The complement system, crosstalk connections, the involvement of complement in clinical conditions and promising therapeutic approaches. Review by Ricklin, Reis and Lambris, free to access for a limited time.

Via Gilbert C FAURE
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Gilbert C FAURE's curator insight, July 9, 1:56 PM
thanks John L
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Structure of Ebola virus’s glycoprotein reveals an Achilles heel 

Structure of Ebola virus’s glycoprotein reveals an Achilles heel  | Host Cell & Pathogen Interactions | Scoop.it

Via Ed Rybicki
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Identification of Zika Virus and Dengue Virus Dependency Factors using Functional Genomics: Cell Reports

Identification of Zika Virus and Dengue Virus Dependency Factors using Functional Genomics: Cell Reports | Host Cell & Pathogen Interactions | Scoop.it
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Homeobox NKX2-3 promotes marginal-zone lymphomagenesis by activating B-cell receptor signalling and shaping lymphocyte dynamics

Homeobox NKX2-3 promotes marginal-zone lymphomagenesis by activating B-cell receptor signalling and shaping lymphocyte dynamics | Host Cell & Pathogen Interactions | Scoop.it
The homeobox NKX2 family of transcriptional factors has been shown to regulate fundamental developmental processes.
Via Gilbert C FAURE
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Virus Hacks Host Genome, Steals CRISPR to Protect Itself

Virus Hacks Host Genome, Steals CRISPR to Protect Itself | Host Cell & Pathogen Interactions | Scoop.it
Viruses have often been described as the ultimate parasite, shedding all of their nonessential parts and leaving behind an extremely efficient genetic transfer apparatus. Phage viruses have evolved to infect various bacteria proficiently and hijack their replication machinery to make more viruses. Yet, this often doesn’t preclude a different virus from concomitantly infecting the same bacterium and competing with or overtaking the original phage invader.


Via Ed Rybicki
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Ed Rybicki's curator insight, June 17, 6:24 AM
HATE the word "hack" in the context of infection: so lazy!
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How Gaming Is Helping Organizations Accelerate Recruitment

How Gaming Is Helping Organizations Accelerate Recruitment | Host Cell & Pathogen Interactions | Scoop.it
Using games to recruit is not a new concept.
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HIV uses a 'molecular iris' to control capsid access

HIV uses a 'molecular iris' to control capsid access | Host Cell & Pathogen Interactions | Scoop.it
HIV hides its genome inside a proteinaceous shell formed by capsid hexamers to evade detection and degradation in the cytosol of host cells; however, the capsid also hinders access of substrates that are essential for reverse transcription, such as deoxynucleoside triphosphates (dNTPs). Thus far, it was unclear how HIV imported dNTPs into the capsid. Jacques et al. now show that a dynamic pore exists in the centre of each capsid hexamer that enables the entry of dNTPs and thereby supports reverse transcription inside the capsid.

The HIV capsid is a conical structure that is formed by a single protein, the capsid protein. Capsid monomers are arranged into a symmetrical hexamer around a central axis and the authors hypothesized that a pore might exist along this axis. However, there was no evidence for such a pore from previous hexamer structures. In fact, previous structures showed that the amino-terminal β-hairpins of each capsid monomer blocked the opening of such a potential pore. When the authors examined this region more closely, including in structures of capsid monomers, they noticed that the β-hairpin is flexible and can assume different conformations by tilting up to 15 Å away from the axis of symmetry. Indeed, when reconstructing a capsid hexamer based on monomer structures with this 'open' β-hairpin conformation, a central pore is formed. The conformational change is likely to depend on the protonation status of a histidine residue at the base of the β-hairpin. This is supported by the observation that structures that were obtained at a high crystallisation pH adopted a closed conformation, whereas structures that were obtained at a low pH adopted an open conformation. Interestingly, at physiological pH, the β-hairpin assumes an intermediate position, indicating high flexibility. Thus, the β-hairpin functions as a 'molecular iris' that controls entry to a central pore in the capsid.


Via Ed Rybicki
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FSU research team makes Zika drug breakthrough - Florida State University News

FSU research team makes Zika drug breakthrough - Florida State University News | Host Cell & Pathogen Interactions | Scoop.it
A team of researchers from Florida State University, Johns Hopkins University and the National Institutes of Health has found existing drug compounds that can both stop Zika from replicating in the body and from damaging the crucial fetal brain cells that lead to birth defects in newborns. One of the drugs is already on the …
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New Virus Breaks The Rules Of Infection

New Virus Breaks The Rules Of Infection | Host Cell & Pathogen Interactions | Scoop.it
A virus is generally like a little ball with a few genes. Now scientists have found one that's broken up into five little balls — as if it were dismembered.

Via Ian M Mackay, PhD
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Viruses 'more dangerous in the morning' - BBC News

Viruses 'more dangerous in the morning' - BBC News | Host Cell & Pathogen Interactions | Scoop.it
Viruses are more dangerous when they infect their victims in the morning, a University of Cambridge study suggests.
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Differential host susceptibility and bacterial virulence factors driving Klebsiella liver abscess in an ethnically diverse population

Differential host susceptibility and bacterial virulence factors driving Klebsiella liver abscess in an ethnically diverse population | Host Cell & Pathogen Interactions | Scoop.it
Hypervirulent Klebsiella pneumoniae is an emerging cause of community-acquired pyogenic liver abscess.
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New approach to severe bacterial infections and sepsis

New approach to severe bacterial infections and sepsis | Host Cell & Pathogen Interactions | Scoop.it
Protein fragment could provide a defense when antibiotics fail | Researchers at Harvard-affiliated Boston Children’s Hospital are looking at new potential avenues for controlling both sepsis and the runaway bacterial infections that provoke it.
Via Gilbert C FAURE
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Gene Regulation, Illustrated

Gene Regulation, Illustrated | Host Cell & Pathogen Interactions | Scoop.it
What are epigenetic modifications, and how might they play out across generations?

Via Dr. Stefan Gruenwald
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Cheap blood test can discriminate between bacterial, viral infections, study finds

Cheap blood test can discriminate between bacterial, viral infections, study finds | Host Cell & Pathogen Interactions | Scoop.it
Researchers at the Stanford University School of Medicine have made an important breakthrough in their ongoing efforts to develop a diagnostic test that can tell health-care providers whether a patient has a bacterial infectio
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Reverse Transcriptase with Proofreading Capabilities Created | The Scientist Magazine®

Reverse Transcriptase with Proofreading Capabilities Created | The Scientist Magazine® | Host Cell & Pathogen Interactions | Scoop.it
Using directed evolution, researchers selected a DNA polymerase to copy RNA into DNA.
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Scientists want to replace lab workhorse E. coli with the world’s fastest-growing bacterium

Scientists want to replace lab workhorse E. coli with the world’s fastest-growing bacterium | Host Cell & Pathogen Interactions | Scoop.it
<i>Vibrio natriegens</i> could save researchers valuable time

Via Gerd Moe-Behrens
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Sandia researchers discover mechanism for Rift Valley fever virus infection - Scienmag

Sandia researchers discover mechanism for Rift Valley fever virus infection - Scienmag | Host Cell & Pathogen Interactions | Scoop.it
LIVERMORE, Calif. -- Viruses can't live without us -- literally. As obligate parasites, viruses need a host cell to survive and grow. Scientists are exploiting this characteristic by developing t..
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