Host Cell & Pathogen Interactions
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Viral Evasion of a Bacterial Suicide System by RNA–Based Molecular Mimicry Enables Infectious Altruism

Viral Evasion of a Bacterial Suicide System by RNA–Based Molecular Mimicry Enables Infectious Altruism | Host Cell & Pathogen Interactions | Scoop.it

Abortive infection, during which an infected bacterial cell commits altruistic suicide to destroy the replicating bacteriophage and protect the clonal population, can be mediated by toxin-antitoxin systems such as the Type III protein–RNA toxin-antitoxin system, ToxIN. A flagellum-dependent bacteriophage of the Myoviridae, ΦTE, evolved rare mutants that “escaped” ToxIN-mediated abortive infection within Pectobacterium atrosepticum. Wild-type ΦTE encoded a short sequence similar to the repetitive nucleotide sequence of the RNA antitoxin, ToxI, from ToxIN. The ΦTE escape mutants had expanded the number of these “pseudo-ToxI” genetic repeats and, in one case, an escape phage had “hijacked” ToxI from the plasmid-borne toxIN locus, through recombination. Expression of the pseudo-ToxI repeats during ΦTE infection allowed the phage to replicate, unaffected by ToxIN, through RNA–based molecular mimicry. This is the first example of a non-coding RNA encoded by a phage that evolves by selective expansion and recombination to enable viral suppression of a defensive bacterial suicide system. Furthermore, the ΦTE escape phages had evolved enhanced capacity to transduce replicons expressing ToxIN, demonstrating virus-mediated horizontal transfer of genetic altruism.

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Host Cell & Pathogen Interactions
Strategies of Microbial Virulence and Host Defense
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Frontiers | Human Intestinal Epithelial Cells Release Antiviral Factors That Inhibit HIV Infection of Macrophages | Immunology

Frontiers | Human Intestinal Epithelial Cells Release Antiviral Factors That Inhibit HIV Infection of Macrophages | Immunology | Host Cell & Pathogen Interactions | Scoop.it
As a rich source of CD4+ T cells and macrophages, the gastrointestinal (GI) tract is a major target site for HIV infection. The interplay between GI resident macrophages and intestinal epithelial cells (IECs) constitutes an important element of GI innate immunity against pathogens. In this study, we investigated whether human IECs have the ability to produce antiviral factors that can inhibit HIV infection of macrophages. We demonstrated that IECs possess functional toll-like receptor 3 (TLR3), the activation of which resulted in induction of key IFN regulatory factors (IRF3 and IRF7), IFN-β, IFN-λ and CC chemokines (MIP-1α, MIP-1β, RANTES), the ligands of HIV entry co-receptor CCR5. In addition, TLR3-activated IECs release exosomes that contained the anti-HIV factors, including IFN stimulated genes (ISGs: ISG15, ISG56, MxB, OAS-1, GBP5, and Viperin) and HIV restriction miRNAs (miRNA-17, miRNA-20, miRNA-28, miRNA-29 family members and miRNA-125b). Importantly, treatment of macrophages with supernatant (SN) from the activated IEC cultures inhibited HIV replication. Further studies showed that IEC SN could also induce the expression of antiviral ISGs and cellular HIV restriction factors (Tetherin and APOBEC3G/3F) in HIV-infected macrophages. These findings indicated that IECs might act as an important element in GI innate immunity against HIV infection/replication.

Via Gilbert C FAURE
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Viruses | Free Full-Text | Inhibition of Zika Virus Replication by Silvestrol

Viruses | Free Full-Text | Inhibition of Zika Virus Replication by Silvestrol | Host Cell & Pathogen Interactions | Scoop.it
The Zika virus (ZIKV) outbreak in 2016 in South America with specific pathogenic outcomes highlighted the need for new antiviral substances with broad-spectrum activities to react quickly to unexpected outbreaks of emerging viral pathogens. Very recently, the natural compound silvestrol isolated from the plant Aglaia foveolata was found to have very potent antiviral effects against the (−)-strand RNA-virus Ebola virus as well as against Corona- and Picornaviruses with a (+)-strand RNA-genome. This antiviral activity is based on the impaired translation of viral RNA by the inhibition of the DEAD-box RNA helicase eukaryotic initiation factor-4A (eIF4A) which is required to unwind structured 5´-untranslated regions (5′-UTRs) of several proto-oncogenes and thereby facilitate their translation. Zika virus is a flavivirus with a positive-stranded RNA-genome harboring a 5′-capped UTR with distinct secondary structure elements. Therefore, we investigated the effects of silvestrol on ZIKV replication in A549 cells and primary human hepatocytes. Two different ZIKV strains were used. In both infected A549 cells and primary human hepatocytes, silvestrol has the potential to exert a significant inhibition of ZIKV replication for both analyzed strains, even though the ancestor strain from Uganda is less sensitive to silvestrol. Our data might contribute to identify host factors involved in the control of ZIKV infection and help to develop antiviral concepts that can be used to treat a variety of viral infections without the risk of resistances because a host protein is targeted.
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2018 LASV sequencing - Lassa virus

2018 LASV sequencing - Lassa virus | Host Cell & Pathogen Interactions | Scoop.it
Nigeria is experiencing a high number of Lassa fever cases this year. A collaboration between the Irrua specialist Teaching Hospital (ISTH), Institute for Lassa Fever Research and Control (ILFRC), Irrua, Edo State, Niger…

Via Ed Rybicki, Chris Upton + helpers
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Together Forever: Bacterial–Viral Interactions in Infection and Immunity

Together Forever: Bacterial–Viral Interactions in Infection and Immunity | Host Cell & Pathogen Interactions | Scoop.it
Most viruses first encounter host cells at mucosal surfaces, which are typically colonized by a complex ecosystem of microbes collectively referred to as the microbiota. Recent studies demonstrate the microbiota plays an important role in mediating host–viral interactions and determining the outcomes of these encounters. This review outlines recently described examples of how bacteria and viruses impact each other particularly during infectious processes. Mechanistically, these effects can be broadly categorized as reflecting direct bacterial–viral interactions and/or involving microbial impacts upon innate and/or adaptive immunity.

Via Cindy
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Activation of Notch-1 in oral epithelial cells by P. gingivalis triggers the expression of the antimicrobial protein PLA 2 -IIA

Activation of Notch-1 in oral epithelial cells by P. gingivalis triggers the expression of the antimicrobial protein PLA 2 -IIA | Host Cell & Pathogen Interactions | Scoop.it
Article

Via Gilbert C FAURE
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Structures of C1-IgG1 provide insights into how danger pattern recognition activates complement

Structures of C1-IgG1 provide insights into how danger pattern recognition activates complement | Host Cell & Pathogen Interactions | Scoop.it
In the classical complement pathway, the C1 initiation complex binds to danger patterns on the surface of microbes or damaged host cells and triggers an immune response. Immunoglobulin G (IgG) antibodies form hexamers on cell surfaces that have high avidity for the C1 complex. Ugurlar et al. used cryo–electron microscopy to show how a hexamer of C1 complexes interacts with the IgG hexamer. Structure-guided mutagenesis revealed how C1 is activated to trigger an immune response.

Science , this issue p. [794][1]

[1]: /lookup/volpage/359/794?iss=6377

Via Gilbert C FAURE
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The T cell antigen receptor: the Swiss army knife of the immune system

The T cell antigen receptor: the Swiss army knife of the immune system | Host Cell & Pathogen Interactions | Scoop.it
The mammalian T cell receptor (TCR) orchestrates immunity by responding to many billions of different ligands that it has never encountered before and cannot adapt to at the protein sequence level

Via Gilbert C FAURE
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Mycobacterium tuberculosis Exploits a Molecular Off Switch of the Immune System for Intracellular Survival

Mycobacterium tuberculosis Exploits a Molecular Off Switch of the Immune System for Intracellular Survival | Host Cell & Pathogen Interactions | Scoop.it
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Via Gilbert C FAURE
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Interactions between Enteric Bacteria and Eukaryotic Viruses Impact the Outcome of Infection

Interactions between Enteric Bacteria and Eukaryotic Viruses Impact the Outcome of Infection | Host Cell & Pathogen Interactions | Scoop.it
Enteric viruses encounter a multitude of environments as they traverse the gastrointestinal tract. The interaction of enteric eukaryotic viruses with members of the host microbiota impacts the outcome of infection. Infection with several enteric viruses is impaired in the absence of the gut microbiota, specifically bacteria. The effects of bacteria on virus biology are diverse. Poliovirus capsid stability and receptor engagement are positively impacted by bacteria and bacterial lipopolysaccharides. Norovirus utilizes histo-blood group antigens produced by enteric bacteria to attach and productively infect B cells. Lipopolysaccharides on the envelope of mouse mammary tumor virus promote a tolerogenic environment that allows for the establishment of viral persistence. Reovirus binds Gram negative and Gram-positive bacteria through bacterial envelope components to enhance virion thermostability. Through the direct engagement of bacteria and bacterial components, viruses evolved diverse ways to impact the outcome of infection.
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Why the government is creating lethal viruses

Why the government is creating lethal viruses | Host Cell & Pathogen Interactions | Scoop.it
The National Institutes of Health lifted a US government ban on making lethal viruses, saying the research is necessary to "develop strategies" against public health threats.
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First-Ever Gene Therapy for Babies with "Bubble Boy" Disease

First-Ever Gene Therapy for Babies with "Bubble Boy" Disease | Host Cell & Pathogen Interactions | Scoop.it
There is a genetic disorder affecting the immune system so severely that its patients often require protective isolation, hence the disease’s nicknam

Via Gilbert C FAURE
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Gene Therapy Hits a Peculiar Roadblock: A Virus Shortage

Gene Therapy Hits a Peculiar Roadblock: A Virus Shortage | Host Cell & Pathogen Interactions | Scoop.it
Revolutionary new treatments depend on tailor-made viruses, but laboratories cannot make them fast enough.
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Zika virus kills brain cancer stem cells - Scienmag: Latest Science and Health News

Zika virus kills brain cancer stem cells - Scienmag: Latest Science and Health News | Host Cell & Pathogen Interactions | Scoop.it
While Zika virus causes devastating damage to the brains of developing fetuses, it one day may be an effective treatment for glioblastoma, a deadly form of brain cancer. New research from Washington University School of Medicine in..

Via Denis Hudrisier
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mRNA vaccines — a new era in vaccinology

mRNA vaccines — a new era in vaccinology | Host Cell & Pathogen Interactions | Scoop.it

Review


mRNA vaccines represent a promising alternative to conventional vaccine approaches, but their application has been hampered by instability and delivery issues. Here, Pardi and colleagues discuss recent advances in mRNA vaccine technology, assess mRNA vaccines currently in development for cancer and infectious diseases and consider future directions and challenges. Abstract


Via Krishan Maggon
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The Immune System In 333 Seconds

Triple III By ATS Created by Mathew Currie, Shalisha Maisrikrod & Natkunam Ketheesan. A collaborative production by Australian Tropical Solutions and One

Via Gilbert C FAURE
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Monkeypox in Central African Republic: ProMed update

Date: Fri 16 Mar 2018 Source: WHO Weekly Bulletin of Outbreaks and Other Emergencies [edited] http://apps.who.int/iris/bitstream/10665/260520/1/OEW11-101632018.pdf During week 9 (week ending 4 Mar 2018), 3 suspected cases of monkeypox were reported in Bria town in Haute-Kotto prefecture. Samples obtained from the 1st 2 cases tested positive for monkeypox at the Institut Pasteur Bangui. Further investigations are ongoing. Public health actions 

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A crisis committee has been revitalized in response to the monkeypox outbreak, being supported by WHO and partners. An isolation unit has been set up in Bria hospital, where the 3 patients are being treated, supported by the NGO IMC. The contacts of these cases are being monitored. Standard case definition for monkeypox has been disseminated to facilitate identification of cases and awareness about prevention is ongoing in the community and on the local community radio. The Ministry of Health is in the process of developing a monkeypox outbreak response plan, following the confirmation of the disease in Bria.


Via Ed Rybicki, Chris Upton + helpers
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A strategy for Helicobacter pylori to attenuate the host immune responses

A strategy for Helicobacter pylori to attenuate the host immune responses | Host Cell & Pathogen Interactions | Scoop.it
Lead researcher This study was led by Dr Le Son Tran and A/Prof Richard Ferrero Main finding The bacterium Helicobacter pylori (H. pylori) infects half of the world’s population and is the main cause of gastric cancer.

Via Gilbert C FAURE
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Pneumocystis and interactions with host immune receptors

Pneumocystis and interactions with host immune receptors | Host Cell & Pathogen Interactions | Scoop.it
Citation: Hoving JC (2018) Pneumocystis and interactions with host immune receptors. PLoS Pathog 14(2): e1006807. https://doi.org/10.1371/journal.ppat.1006807 Editor: Donald C. Sheppard, McGill University, CANADA Published: February 22, 2018 Copyright: © 2018 Jennifer Claire Hoving.

Via Gilbert C FAURE
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The Transcription Factor STAT6 Mediates Direct Repression of Inflammatory Enhancers and Limits Activation of Alternatively Polarized Macrophages

The molecular bases of repressive transcriptional mechanisms contributing to macrophage
polarization are not well understood. Czimmerer et al. show that in alternatively
polarized macrophages, IL-4-activated STAT6 represses a large set of enhancers modulating
the transcriptional program. STAT6-repressed enhancers are characterized by reduced
chromatin accessibility, eRNA expression, LDTF, and p300 binding. IL-4-STAT6-mediated
repression limits the inflammatory responsiveness including inflammasome activation,
IL-1β production, and pyroptosis. Thus, the IL4-STAT6 pathway establishes an epigenomic
signature to selectively repress the macrophage inflammation program.

Via Gilbert C FAURE
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Construction of an infectious horsepox virus vaccine from chemically synthesized DNA fragments

Construction of an infectious horsepox virus vaccine from chemically synthesized DNA fragments | Host Cell & Pathogen Interactions | Scoop.it

Edward Jenner and his contemporaries believed that his variolae vaccinae originated in horses and molecular analyses show that modern vaccinia virus (VACV) strains share common ancestry with horsepox virus (HPXV). Given concerns relating to the toxicity of modern VACV vaccines, we asked whether an HPXV-based vaccine might provide a superior alternative. Since HPXV may be extinct and the only specimen of HPXV that has been identified is unavailable for investigation, a group of scientists now explored whether HPXV could be obtained by large-scale gene synthesis.

 

Ten large (10–30 kb) fragments of DNA were synthesized based on the HPXV sequence along with two 157 nt VACV terminal sequences, and were recombined into a live synthetic chimeric HPXV (scHPXV) in cells infected with Shope fibroma virus (SFV). Sequencing of the 212 kbp scHPXV confirmed it encoded a faithful copy of the input DNA.

 

This is the first complete synthesis of a poxvirus using synthetic biology approaches. This scHPXV produced smaller plaques, produced less extracellular virus and exhibited less virulence in mice than VACV, but still provided vaccine protection against a lethal VACV challenge. Collectively, these findings support further development of scHPXV as a novel replication-proficient smallpox vaccine.


Via Dr. Stefan Gruenwald
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How good bacteria control your genes

How good bacteria control your genes | Host Cell & Pathogen Interactions | Scoop.it

Signals produced by bacteria in the gut could help prevent infections and bowel cancer


Via Integrated DNA Technologies
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Frontiers | Type I Interferons in the Pathogenesis of Tuberculosis: Molecular Drivers and Immunological Consequences | Immunology

Frontiers | Type I Interferons in the Pathogenesis of Tuberculosis: Molecular Drivers and Immunological Consequences | Immunology | Host Cell & Pathogen Interactions | Scoop.it
Tuberculosis (TB) remains a major global health threat. Urgent needs in the fight against TB include improved and innovative treatment options for drug-sensitive and -resistant TB as well as reliable biological indicators that discriminate active from latent disease and enable monitoring of treatment success or failure. Prominent interferon (IFN) inducible gene signatures in TB patients and animal models of M. tuberculosis infection have drawn significant attention to the roles of type I IFNs in the host response to mycobacterial infections. Here we review recent developments in the understanding of the innate immune pathways that drive type I IFN responses in mycobacteria-infected host cells and the functional consequences for the host defense against M. tuberculosis, with a view that such insights might be exploited for the development of targeted host-directed immunotherapies and development of reliable biomarkers.

Via Gilbert C FAURE
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The twilight of immunity: emerging concepts in aging of the immune system

The twilight of immunity: emerging concepts in aging of the immune system | Host Cell & Pathogen Interactions | Scoop.it
Review Article

Via Gilbert C FAURE, Kenzibit
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Vaginal lactic acid elicits an anti-inflammatory response from human cervicovaginal epithelial cells and inhibits production of pro-inflammatory mediators associated with HIV acquisition

Vaginal lactic acid elicits an anti-inflammatory response from human cervicovaginal epithelial cells and inhibits production of pro-inflammatory mediators associated with HIV acquisition | Host Cell & Pathogen Interactions | Scoop.it
Article Report

Via Gilbert C FAURE
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Viral unmasking of cellular 5S rRNA pseudogene transcripts induces RIG-I-mediated immunity

Article

Via Denis Hudrisier
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