Virology and Bioinformatics from Virology.ca
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Virology and Bioinformatics from Virology.ca
Virus and bioinformatics articles with some microbiology and immunology thrown in for good measure
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Global Organization of a Positive-strand RNA Virus Genome

Global Organization of a Positive-strand RNA Virus Genome | Virology and Bioinformatics from Virology.ca | Scoop.it

The genomes of many important pathogenic viruses are made of RNA. These genomes encode viral proteins and contain regulatory sequences and structures. In some viruses, distant regions of the RNA genome can interact with each other via base pairing, which suggests that certain genomes may take on well-defined conformations. This concept was investigated using a tombusvirus RNA genome that contains several long-range RNA interactions. The results of microscopic and biochemical analyses indicated a compact genome conformation with structured regions radiating from a central core. The structural model was compatible with some, but not all, long-range interactions, suggesting that the genome is a dynamic molecule that assumes different conformations. The analysis also revealed new structural features of the genome, some of which were shown to be functionally relevant. This study advances our understanding of the role played by global structure in virus genome function and provides a model to further investigate its in role virus reproduction. We anticipate that organizational principles revealed by this investigation will be applicable to other viruses.

  
Ed Rybicki's insight:

Plant viruses rule OK...!  Or biophysical investigations of their genomes do.  Seriously, this is an impressive piece of work, that points up the fact that information content of a genome definitely does not stop with the sequence.

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Infectivity, Transmission, and Pathology of Human H7N9 Influenza in Ferrets and Pigs

The emergence of the H7N9 influenza virus in humans in Eastern China has raised concerns that a new influenza pandemic could occur. Here, we used a ferret model to evaluate the infectivity and transmissibility of A/Shanghai/2/2013 (SH2), a human H7N9 virus isolate. This virus replicated in the upper and lower respiratory tracts of the ferrets and was shed at high titers for 6 to 7 days, with ferrets showing relatively mild clinical signs. SH2 was efficiently transmitted via direct contact, but less efficiently by airborne exposure. Pigs could be productively infected by SH2 and shed virus for 6 days but were unable to transmit the virus to other animals. Under appropriate conditions human-to-human transmission of the H7N9 virus may be possible.

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PLOS ONE: Into the Wild: Dissemination of Antibiotic Resistance Determinants via a Species Recovery Program

PLOS ONE: Into the Wild: Dissemination of Antibiotic Resistance Determinants via a Species Recovery Program | Virology and Bioinformatics from Virology.ca | Scoop.it

Management strategies associated with captive breeding of endangered species can establish opportunities for transfer of pathogens and genetic elements between human and animal microbiomes. The class 1 integron is a mobile genetic element associated with clinical antibiotic resistance in gram-negative bacteria. We examined the gut microbiota of endangered brush-tail rock wallabies Petrogale penicillata to determine if they carried class 1 integrons. No integrons were detected in 65 animals from five wild populations. In contrast, class 1 integrons were detected in 48% of fecal samples from captive wallabies. The integrons contained diverse cassette arrays that encoded resistance to streptomycin, spectinomycin, and trimethoprim. Evidence suggested that captive wallabies had acquired typical class 1 integrons on a number of independent occasions, and had done so in the absence of strong selection afforded by antibiotic therapy. Sufficient numbers of bacteria containing diverse class 1 integrons must have been present in the general environment occupied by the wallabies to account for this acquisition. The captive wallabies have now been released, in an attempt to bolster wild populations of the species. Consequently, they can potentially spread resistance integrons into wild wallabies and into new environments. This finding highlights the potential for genes and pathogens from human sources to be acquired during captive breeding and to be unwittingly spread to other populations.

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Self-assembling influenza nanoparticle vaccines elicit broadly neutralizing H1N1 antibodies

Influenza viruses pose a significant threat to the public and are a burden on global health systems1, 2. Each year, influenza vaccines must be rapidly produced to match circulating viruses, a process constrained by dated technology and vulnerable to unexpected strains emerging from humans and animal reservoirs. Here we use knowledge of protein structure to design self-assembling nanoparticles that elicit broader and more potent immunity than traditional influenza vaccines. The viral haemagglutinin was genetically fused to ferritin, a protein that naturally forms nanoparticles composed of 24 identical polypeptides3. Haemagglutinin was inserted at the interface of adjacent subunits so that it spontaneously assembled and generated eight trimeric viral spikes on its surface. Immunization with this influenza nanoparticle vaccine elicited haemagglutination inhibition antibody titres more than tenfold higher than those from the licensed inactivated vaccine. Furthermore, it elicited neutralizing antibodies to two highly conserved vulnerable haemagglutinin structures that are targets of universal vaccines: the stem4, 5 and the receptor binding site on the head6, 7. Antibodies elicited by a 1999 haemagglutinin–nanoparticle vaccine neutralized H1N1 viruses from 1934 to 2007 and protected ferrets from an unmatched 2007 H1N1 virus challenge. This structure-based, self-assembling synthetic nanoparticle vaccine improves the potency and breadth of influenza virus immunity, and it provides a foundation for building broader vaccine protection against emerging influenza viruses and other pathogens.

  
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PLOS ONE: The Influenza Virus Protein PB1-F2 Interacts with IKKβ and Modulates NF-κB Signalling

PLOS ONE: The Influenza Virus Protein PB1-F2 Interacts with IKKβ and Modulates NF-κB Signalling | Virology and Bioinformatics from Virology.ca | Scoop.it
Abstract

"PB1-F2, a protein encoded by a second open reading frame of the influenza virus RNA segment 2, has emerged as a modulator of lung inflammatory responses but the molecular mechanisms underlying this are only poorly understood. Here we show that PB1-F2 inhibits the activation of NF-κB dependent signalling pathways in luciferase reporter assays. PB1-F2 proteins from four different viruses interact with IKKβ in yeast two-hybrid assays and by co-immunoprecipitation. PB1-F2 expression did not inhibit IKKβ kinase activity or NF-κB translocation into the nucleus, but NF-κB binding to DNA was severely impaired in PB1-F2 transfected cells as assessed by Electrophoretic Mobility Shift Assay. Neither the N-terminal 57 amino acid truncated forms nor the C-terminus of PB1-F2 were able to inhibit NF-κB dependent signalling, indicating that the full length protein is necessary for the inhibition."

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Recombination within the pandemic norovirus GII.4 lineage

Recombination within the pandemic norovirus GII.4 lineage | Virology and Bioinformatics from Virology.ca | Scoop.it

Norovirus (NoV) is the leading cause of viral gastroenteritis globally. Since 1996, variants of a single genetic lineage, NoV GII.4, have been associated with at least five pandemics of acute gastroenteritis and caused between 62-80% of all NoV outbreaks. The emergence of these novel GII.4 variants has been attributed to rapid evolution and antigenic variation in response to herd immunity; however the contribution of recombination as a mechanism facilitating emergence is increasingly evident.

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Bacteriophage adhering to mucus provide a non–host-derived immunity

Bacteriophage adhering to mucus provide a non–host-derived immunity | Virology and Bioinformatics from Virology.ca | Scoop.it

Mucosal surfaces are a main entry point for pathogens and the principal sites of defense against infection. Both bacteria and phage are associated with this mucus. Here we show that phage-to-bacteria ratios were increased, relative to the adjacent environment, on all mucosal surfaces sampled, ranging from cnidarians to humans. In vitro studies of tissue culture cells with and without surface mucus demonstrated that this increase in phage abundance is mucus dependent and protects the underlying epithelium from bacterial infection.

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Goodbye smallpox vaccination, hello monkeypox

Goodbye smallpox vaccination, hello monkeypox | Virology and Bioinformatics from Virology.ca | Scoop.it

In 8 May 1980, the World Health Organisation declared that “the world and its peoples are free from smallpox.” Through decades of intense vaccination, this once fatal disease had been wiped out. It was a singular victory and having won it, countries around the world discontinued the vaccination programmes. After all, why protect against a disease that no longer exists, except in a few isolated stocks?

 

Unfortunately, this is not a rhetorical question. The smallpox vaccine did more than protect against smallpox. It also reduced the risk of contracting a related illness called monkeypox, which produces the same combination of scabby bumps and fever. It’s milder than smallpox but it’s still a serious affliction. In Africa, where monkeypox originates from, it kills anywhere from 1-10% of those who are infected. And more and more people are becoming infected.

 

Anne Rimoin from the University of California, Los Angeles compared data on the virus in the Democratic Republic of Congo over the last three decades. She found that, during those years, monkeypox has become 20 times more common in humans. In one particular area, 72 people out of every million were infected each year between 1981 and 1986. Between 2005 and 2007, that figure rose to 1442 per million. Rimoin thinks that we eased up the pressure on smallpox vaccination too soon. Between 1981 and 1985, only 404 cases turned up in all of Africa, and simulations predicted that the disease was unlikely to spread too far in a human population before dying out. This was no public health threat. In 1986, even the monitoring programme was stopped. In 2005 however, Rimoin’s group, together with the DRC Ministry of Health and the World Health Organization set up a new round of monkeypox surveillance and they spent two years collecting data. Their research showed that the disease is gaining ground.

 

Rimoin found that monkeypox was disproportionately affecting children and almost all of those who fell sick were born after 1980, when the smallpox vaccination programme was halted in the DRC. The vaccine wasn’t a perfect defence against monkeypox but it was still around 85% effective. Among people who were born during the vaccination era, those who were immunised were 5 times less likely to develop monkeypox than their protected peers. And this protection is clearly long-lasting; even 25 years on, they could still ward off the related virus.

 

These figures are probably underestimates too. The region’s inconsistent healthcare isn’t exactly conducive to accurate disease monitoring and Rimoin says that her team had word of many more cases, but couldn’t always check them out because of their remote location.

 

Monkeypox is spread by animals including squirrels and, fairly obviously, monkeys. As humans encroach upon the DRC’s tropical rainforests, the risk of being exposed to an infected carrier grows. Indeed, Rimoin found that the odds of contracting monkeypox were higher for people living near forested areas, and for men. As civil strife continues to affect the DRC, locals are being forced to rely more on hunting to get enough food and that brings men in close contact with furry viral reservoirs.

 

It’s an emerging threat, but Rimoin isn’t calling for smallpox vaccination to resume. Doing so would be logistically difficult in an area where even collecting data can be fraught. It might be better to take a more targeted approach, vaccinating only health workers who treat infected patients, and people who come into frequent contact with animal carriers. It may also be worth educating local people about the dangers of handling carrier species and the benefits of isolating people who show the very obvious symptoms, until they can be treated.

 

But most importantly, Rimoin wants active surveillance in regions where the virus circulates, especially since there are still so many unknowns about the virus. We need to better understand how it moves from human to human (and from animal to human), how often it’s fatal, or what the complications are.

 

It’s a good opportunity to take action now, at a time when the monkeypox is still confined to specific areas. Things might not stay that way. In 2003, there was a bizarre outbreak in the United States, as rodents from Ghana brought the disease to American prairie dogs, who handed it over to humans. All sorts of rodents the world over might become reservoirs for the disease and Rimoin writes, “If monkeypox were to become established in a wildlife reservoir outside Africa, the public health setback would be difficult to reverse.”


Via Dr. Stefan Gruenwald
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PLOS Computational Biology: A Universal Trend among Proteomes Indicates an Oily Last Common Ancestor

PLOS Computational Biology: A Universal Trend among Proteomes Indicates an Oily Last Common Ancestor | Virology and Bioinformatics from Virology.ca | Scoop.it

Notably, the evidence presented (a) indicates that proteomes of all species ranging from bacteria to mammals appear to adhere to the same universal constraint (“oil escape”) set into motion by the last common ancestor more than 3.5 billion years ago, (b) indicates the presence of a previously untapped global (composition-level) molecular clock, and (c) strengthens the non-equilibrium/directional view of amino acid substitutions that challenges central dogmas regarding reversibility in molecular evolution.

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Human monoclonal ScFv that bind to different functional domains of M2 and inhibit H5N1 influenza virus replication Virol J. 2013

BACKGROUND:

Novel effective anti-influenza agent that tolerates influenza virus antigenic variation is needed. Highly conserved influenza virus M2 protein has multiple pivotal functions including ion channel activity for vRNP uncoating, anti-autophagy and virus assembly, morphogenesis and release. Thus, M2 is an attractive target of anti-influenza agents including small molecular drugs and specific antibodies.

METHODS:

Fully human monoclonal single chain antibodies (HuScFv) specific to recombinant and native M2 proteins of A/H5N1 virus were produced from huscfv-phagemid transformed E. coli clones selected from a HuScFv phage display library using recombinant M2 of clade 1 A/H5N1 as panning antigen. The HuScFv were tested for their ability to inhibit replication of A/H5N1 of both homologous and heterologous clades. M2 domains bound by HuScFv of individual E. coli clones were identified by phage mimotope searching and computerized molecular docking.

RESULTS:

HuScFv derived from four huscfv-phagemid transformed E. coli clones (no. 2, 19, 23 and 27) showed different amino acid sequences particularly at the CDRs. Cells infected with A/H5N1 influenza viruses (both adamantane sensitive and resistant) that had been exposed to the HuScFv had reduced virus release and intracellular virus. Phage peptide mimotope search and multiple alignments revealed that conformational epitopes of HuScFv2 located at the residues important for ion channel activity, anti-autophagy and M1 binding; epitopic residues of HuScFv19 located at the M2 amphipathic helix and cytoplasmic tail important for anti-autophagy, virus assembly, morphogenesis and release; epitope of HuScFv23 involved residues important for the M2 activities similar to HuScFv2 and also amphipathic helix residues for viral budding and release while HuScFv27 epitope spanned ectodomain, ion channel and anti-autophagy residues. Results of computerized homology modelling and molecular docking conformed to the epitope identification by phages.

CONCLUSIONS:

HuScFv that bound to highly conserved epitopes across influenza A subtypes and human pathogenic H5N1clades located on different functional domains of M2 were produced. The HuScFv reduced viral release and intracellular virus of infected cells. While the molecular mechanisms of the HuScFv await experimental validation, the small human antibody fragments have high potential for developing further as a safe, novel and mutation tolerable anti-influenza agent especially against drug resistant variants.

 
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PLOS ONE: Malaria Infected Mosquitoes Express Enhanced Attraction to Human Odor

PLOS ONE: Malaria Infected Mosquitoes Express Enhanced Attraction to Human Odor | Virology and Bioinformatics from Virology.ca | Scoop.it

Abstract

There is much evidence that some pathogens manipulate the behaviour of their mosquito hosts to enhance pathogen transmission. However, it is unknown whether this phenomenon exists in the interaction of Anopheles gambiae sensu stricto with the malaria parasite, Plasmodium falciparum - one of the most important interactions in the context of humanity, with malaria causing over 200 million human cases and over 770 thousand deaths each year. Here we demonstrate, for the first time, that infection with P. falciparum causes alterations in behavioural responses to host-derived olfactory stimuli in host-seeking female An. gambiae s.s. mosquitoes.

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Cloning produces human embryonic stem cells | Genes & Cells | Science News

Cloning produces human embryonic stem cells | Genes & Cells | Science News | Virology and Bioinformatics from Virology.ca | Scoop.it

For the first time, scientists have created human embryonic stem cells by transferring the nucleus of a mature cell into an egg. The cloning technique could nudge the dream of personalized medicine closer to reality, researchers suggest May 15 in Cell.

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Immunization with Biodegradable Nanoparticles Efficiently Induces Cellular Immunity and Protects against Influenza Virus Infection

Immunization with Biodegradable Nanoparticles Efficiently Induces Cellular Immunity and Protects against Influenza Virus Infection | Virology and Bioinformatics from Virology.ca | Scoop.it

The ability of vaccines to induce T cell responses is crucial for preventing diseases caused by viruses or bacteria. Nanoparticles (NPs) are considered an efficient tool for inducing potent immune responses. In this study, we describe a novel vaccination approach with biodegradable calcium phosphate (CaP) NPs that serve as carrier of immunoactive TLR9 ligand (CpG) combined with a viral Ag from the influenza A virus hemagglutinin. Functionalized CaP NPs were efficiently taken up by dendritic cells in vivo and elicited a potent T cell–mediated immune response in immunized mice with high numbers of IFN-γ–producing CD4+ and CD8+ effector T cells. Most importantly, both i.p. and intranasal immunization with these NPs offered protection in a mouse model of influenza virus infection. This study demonstrates the great potential of CaP NPs as a novel vaccination tool that offers substantial flexibility for several infection models.

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Virophages, polintons, and transpovirons: a complex evolutionary network of diverse selfish genetic elements with different reproduction strategies

Virophages, polintons, and transpovirons: a complex evolutionary network of diverse selfish genetic elements with different reproduction strategies | Virology and Bioinformatics from Virology.ca | Scoop.it

The results of the phylogenomic analysis of the virophages and related genetic elements are compatible with the concept of network-like evolution of the virus world and emphasize multiple evolutionary connections between bona fide viruses and other classes of capsid-less mobile elements.

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Ed Rybicki's curator insight, May 24, 2013 9:26 AM

Blow your MINDS, virologists...deep relationships between phages, human viruses, satellite viruses and big DNA viruses - as well as with diverse mobile elements within genomes.

Ignacio López-Goñi's curator insight, May 25, 2013 3:50 AM

Apasionante: el tema se complica! 

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Virology Journal | Abstract | Boginia virus, a newfound hantavirus harbored by the Eurasian water shrew (Neomys fodiens) in Poland

Guided by decades-old reports of hantaviral antigens in the Eurasian common shrew (Sorex araneus) and the Eurasian water shrew (Neomys fodiens) in European Russia, we employed RT-PCR to analyze lung tissues of soricine shrews, captured in Boginia,...
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Microbe mind control

Microbe mind control | Virology and Bioinformatics from Virology.ca | Scoop.it
Last week, there was media coverage of a paper published in PLoS pathogens. The study found Plasmodium falciparum - the parasite which causes malaria - makes their mosquito host more attracted to human body odour compared to uninfected mosquitoes.
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Emerging Microbes & Infections - Virus ecology: a gap between detection and prediction

Emerging Microbes & Infections - Virus ecology: a gap between detection and prediction | Virology and Bioinformatics from Virology.ca | Scoop.it
Emerging Microbes and Infections (EMI) is a new open access, fully peer-reviewed journal that will publish the best and most interesting research in emerging microbes and infectious disease.

The past few months have yielded disconcerting news about viruses carried in mammalian reservoirs. What is the relevance of virus discoveries mushrooming in the literature? Will bats yield the next pandemic virus? Animal ecologists and virologists need to join forces.

 
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The prospects and challenges of universal vaccines for influenza - Trends in Microbiology

Vaccination is the most effective way to reduce the impact of epidemic as well as pandemic influenza. However, the licensed inactivated influenza vaccine induces strain-specific immunity and must be updated annually. When novel viruses appear, matched vaccines are not likely to be available in time for the first wave of a pandemic. Yet, the enormous diversity of influenza A viruses in nature makes it impossible to predict which subtype or strain will cause the next pandemic. Several recent scientific advances have generated renewed enthusiasm and hope for universal vaccines that will induce broad protection from a range of influenza viruses.

 
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The end of H7N9? No new bird flu cases reported in over a week

The end of H7N9? No new bird flu cases reported in over a week | Virology and Bioinformatics from Virology.ca | Scoop.it
After months of mounting concern, Chinese health officials are breathing a sigh of relief: no new human cases of H7N9 have been reported in the country in more than a week. The milestone marks the... (RT @verge: The end of H7N9?
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Open reading frame phylogenetic analysis on t... [Int J Genomics. 2013] - PubMed - NCBI

Open reading frame phylogenetic analysis on t... [Int J Genomics. 2013] - PubMed - NCBI | Virology and Bioinformatics from Virology.ca | Scoop.it
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PLOS Pathogens: The Secret Life of Viral Entry Glycoproteins: Moonlighting in Immune Evasion

PLOS Pathogens: The Secret Life of Viral Entry Glycoproteins: Moonlighting in Immune Evasion | Virology and Bioinformatics from Virology.ca | Scoop.it
From molecules to physiology
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PLOS ONE: Pandemic H1N1 Influenza Isolated from Free-Ranging Northern Elephant Seals in 2010 off the Central California Coast

PLOS ONE: Pandemic H1N1 Influenza Isolated from Free-Ranging Northern Elephant Seals in 2010 off the Central California Coast | Virology and Bioinformatics from Virology.ca | Scoop.it
Abstract

Interspecies transmission of influenza A is an important factor in the evolution and ecology of influenza viruses. Marine mammals are in contact with a number of influenza reservoirs, including aquatic birds and humans, and this may facilitate transmission among avian and mammalian hosts. Virus isolation, whole genome sequencing, and hemagluttination inhibition assay confirmed that exposure to pandemic H1N1 influenza virus occurred among free-ranging Northern Elephant Seals (Mirounga angustirostris) in 2010. Nasal swabs were collected from 42 adult female seals in April 2010, just after the animals had returned to the central California coast from their short post-breeding migration in the northeast Pacific.

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MicroMicrobe •  Microbial image of the month This is a great...

MicroMicrobe •  Microbial image of the month This is a great... | Virology and Bioinformatics from Virology.ca | Scoop.it
 Microbial image of the month


This is a great image of a biofilm growing on a micro-fibrous material. Biofilms are aggregates of bacteria that are coated with a ‘slimy’ substance consisting of polysaccharide, DNA and proteins.
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'MERS' Makes Its Debut in a Scientific Journal - ScienceInsider

'MERS' Makes Its Debut in a Scientific Journal - ScienceInsider | Virology and Bioinformatics from Virology.ca | Scoop.it

A group of coronavirus experts has published its proposal to name a new, deadly virus after the Middle East, the region where it originates. In a short paper published online today by the Journal of Virology, the Coronavirus Study Group (CSG), along with several other scientists, recommends calling the pathogen Middle East Respiratory Syndrome Coronavirus (MERS-Cov).

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Heterogenous nuclear ribonucleoprotein Q increases protein expression from HIV-1 Rev dependent transcripts.

Heterogenous nuclear ribonucleoproteins (hnRNPs) control many processes of the gene expression machinery including mRNA transcription, splicing, export, stability and translation.
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