Bluetongue is a severe disease of ruminants, notably sheep and cattle. The causal agent, the dsRNA Bluetongue virus, is spread by an insect vector and occurs in its vector’s habitat in temperate climates throughout much of the world. BTV is the type member of genus Orbivirus in the family Reoviridae, with 26 known serotypes. When bluetongue first broke out in the United Kingdom in autumn of 2007, the disease was already rapidly spreading throughout continental Europe, causing high mortality rates in sheep and having a detrimental effect on the livestock trade through trade restrictions and loss of stock. The only effective weapon against the disease is control of the spread of BTV through rigorous vaccination programmes. Currently available commercial vaccines are based on both inactivated virus and live, attenuated strains and protect against a single serotype or multiple serotypes when provided as a cocktail. However, the possibility of recombination between the live vaccine strain(s) and wild-type virus in infected animals, leading to the emergence of new infectious strains has motivated efforts to develop safer vaccines.

One approach in the development of an inherently safe vaccine has been the production of Bluetongue virus-like particles (VLPs). BTV has a nonenveloped icosahedral structure, with four main structural proteins (VP3, VP7, VP5 and VP2) arranged in concentric shells around the segmented double-stranded RNA genome and minor structural and nonstructural proteins involved in virus replication. French et al. have shown that these four structural proteins, expressed in insect cells using a baculovirus expression system, assemble into virus-like particles devoid of nucleic acid.

This paper describes plant-based high-level expression of assembled subcore-, core- and virus-like particles of BTV serotype 8. Purified preparations of the VLPs, consisting of all four structural proteins, elicited an immune response in sheep and provided protective immunity against challenge with a South African BTV-8 field isolate. This demonstrates that plant expression provides an economically viable method for producing complex VLPs, such as those of BTV, with the desired biological properties. It represents a significant advance in the use of plant-based systems for the production of complex biopharmaceuticals. The methods employed could also be applied to other situations where the expression of multiple proteins is required, such as the reconstruction of metabolic pathways.

A method for rapid production of heteromultimeric protein complexes in plants: assembly of protective bluetongue virus-like particles. Plant Biotechnol J. 06 May 2013 doi: 10.1111/pbi.12076
Plant expression systems based on nonreplicating virus-based vectors can be used for the simultaneous expression of multiple genes within the same cell. They therefore have great potential for the production of heteromultimeric protein complexes. This work describes the efficient plant-based production and assembly of Bluetongue virus-like particles (VLPs), requiring the simultaneous expression of four distinct proteins in varying amounts. Such particles have the potential to serve as a safe and effective vaccine against Bluetongue virus (BTV), which causes high mortality rates in ruminants and thus has a severe effect on the livestock trade. Here, VLPs produced and assembled in Nicotiana benthamiana using the cowpea mosaic virus-based HyperTrans (CPMV-HT) and associated pEAQ plant transient expression vector system were shown to elicit a strong antibody response in sheep. Furthermore, they provided protective immunity against a challenge with a South African BTV-8 field isolate. The results show that transient expression can be used to produce immunologically relevant complex heteromultimeric structures in plants in a matter of days. The results have implications beyond the realm of veterinary vaccines and could be applied to the production of VLPs for human use or the coexpression of multiple enzymes for the manipulation of metabolic pathways.

Feet Are a Treat for Fungi

Smelly, itchy feet are constant reminders that we share our bodies with fungi. But just how many and what kinds? A new genetic survey has uncovered an incredible diversity of fungi on the feet, with different communities in the heel, toenail, and space between the third and fourth toes. The bottom of the heel alone hosts 80 different types, and if cataloged by species, the tally would likely be an order of magnitude higher. Fungi in each of these communities were similar from one person to the next, except in a woman who had a persistent toenail infection: She had lots of other fungi not found on the other nine people, indicating that more kinds of fungi could take up residence in the feet if they had the opportunity…

Bacterium excluded from the Eukaryote Club

It’s something you learn in high school – there are two basic approaches to cellular life – prokaryotes (bacteria and archaea) and eukaryotes (the rest of us – aardvarks, amoebae, apricots, etc). Prokaryotes have an open-plan office, with all biological functions carried out in the one cellular space. Eukaryotes, however, have dedicated compartments for the chief executive(nucleus), finance (mitochondria), sales and marketing (golgi,endoplasmic reticulum), and so on.

But every now and then you get an upstart prokaryote that seems to have ideas above its station. One such is Gemmata obscuriglobus, an exemplar of a bunch of unusual bugs known as the PVC superphylum (for Planctomycetes, Verrucomicrobiae, Chlamydiae). Gemmata has a complex membrane structure, and previous studies of its 3D configuration have suggested that this bacterium has a compartmentalised cell, eukaryote-style, its genetic material encapsulated in a nucleus-like body.

With a nice combination of technical wizardry and sheer hard work, Rachel Santarella-Mellwig,Damien Devos and colleagues, authors of a paper just published in PLOS Biology, have managed to reconstruct the structure of the internal membranes of a typical Gemmata cell in spectacular detail. They embedded ten bugs in plastic, chopped them each into ten or so slices, and then took electron microscope snapshots of the Gemmata salami. In the absence of software that could do the job, they then manually tracked and assigned the membranes in each slice, building up a detailed 3D model of the membranes and other features.

The answer, perhaps sadly, is that Gemmatais actually rather a traditional bug, topologically speaking. The beautiful pictures and movies produced by the authors reveal a membrane system that, while extremely convoluted, doesn’t enclose any separate compartments. Gemmata is as prokaryotic as they come.

Latest News | W.H.O. Global Alert and Response

1. Coronaviruses are a family of viruses that includes viruses that may cause a range of illnesses in humans, from common cold-type respiratory infections to SARS. Viruses of this family also cause a number of animal diseases.

2. What’s it called again?
Currently being referred to as nCoV or nCoV-2012, this virus has also been called Human Coronavirus-Erasmus Medical Center (hCoV-EMC), or Middle East respiratory syndrome coronavirus (MERS-CoV), and even “Saudi SARS” (it’s not – SARS is a related but different Coronavirus).

3. The first known case of nCoV infection was in a Saudi Arabian man who died in early 2012. This particular strain of coronavirus had not been previously identified in humans. The second confirmed case appeared in early September 2012, involving a 49-year old man in Doha, Qatar who had traveled to Saudi Arabia around the same time that the first case was identified. Currently, at least 40 cases have been confirmed, and 20 of those affected have died. The virus has also been found in Tunisia.

4. Where did it come from?
Bats. (It’s [nearly] always bats.) Bat coronaviruses carried by the genus Pipistrellus that differ from nCoV by as little as 1.8%. The existence of over 50 species of Pipistrellus bats in the Arabian Peninsula suggests that they may be the animal reservoir.

5. Symptoms of nCoV infection include renal failure and severe acute pneumonia, which often result in a fatal outcome. In humans, the virus has a strong tropism for nonciliated bronchial epithelial cells because it uses dipeptidyl peptidase 4 (DPP4, also known as CD26) as a receptor.

6. nCoV can penetrate the bronchial epithelium and evade the innate immune system, signs that it is well-equipped for infecting human cells. This suggests that although nCoV may have jumped from animals to humans very recently, it is as well adapted to infecting the human respiratory tract as other, more familiar human coronaviruses, including the SARS virus and the common cold Coronavirus HCoV-229E.

7. The virus is susceptible to treatment with interferons, immune proteins that have been used successfully to treat other viral diseases, offering a possible method of treatment in the event of a large-scale outbreak.

8. How is it transmitted?
Almost certainly like other respiratory viruses, via aerosol droplets from coughs and sneezes, but possibly also by unwashed hands contaminated with respiratory secretions.

9. Is there a vaccine?
Not yet. It is possible to make vaccines agains Coronaviruses and several SARS vaccines were developed but never put into use because the SARS outbreak died away. It should be possible to make a nCoV vaccine if we need one.

10. Is there any travel advice?
At the moment the World Health Organization says there is no reason to impose any travel restrictions. Travel advice will be kept under review if additional cases occur or when the patterns of transmission become clearer.

11. Are we all going to die?
Probably not. Most of the people who have been infected so far have been older men, often with other medical conditions. The outbreak of Severe Acute Respiratory Syndrome (SARS) in 2003 infected over 8000 people and killed nearly 800 before burning itself out. But SARS didn’t kill us all and it’s unlikely that nCoV will either.

Other things you should know:

• 10 things you should know about H1N1 (swineflu)
• 10 things you should know about E. coli
• 10 things you didn’t know about Schmallenberg virus
• 10 things about Foot and Mouth Disease

Tamiflu drug bill “shocking waste of taxpayers’ money”?

Uh, yeah, you wouldn’t be saying that if the swine flu pandemic hadn’t turned out to be as mild as it was. 

The prospects and challenges of universal vaccines for influenza

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.

Trends Microbiol. 2013 May 16. pii: S0966-842X(13)00074-7. doi: 10.1016/j.tim.2013.04.003

Irish potato famine mystery solved after 168 years

Scientists believe they have finally identified the pathogen that caused the Irish potato famine. BBC News reports a research team led by The Sainsbury Laboratory in Norwich, England, used dried leaf cuttings — some of which are nearly 170 years old — to reconstruct the spread of the HERB-1 strain of Phytophthora infestans, a fungal disease that came to Ireland via Mexico in 1845. The disease destroyed potato crops and caused the deaths of a million people.

Schmallenberg vaccine available to UK farmers this summer

Vaccine will prevent a disease that causes severe birth defects and miscarriages in livestock.

All about Schmallenberg virus: http://goo.gl/fuPyT

A new vaccine is being made available to prevent a disease which causes severe birth defects and miscarriages in livestock. Schmallenberg virus, which emerged in the Netherlands and Germany in 2011 and has been seen in cattle and sheep in the UK since early 2012, has been identified on more than 1,700 farms across the country. Adult animals infected during pregnancies in the autumn by virus-carrying midges, thought to have blown across the Channel, have given birth to deformed or stillborn lambs and calves.  UK farmers are the first in the European Union to have access to a vaccine against Schmallenberg, which will be available for vaccinating livestock this summer before most animals become pregnant again.

Friendly Viruses Protect Us Against Bacteria

One of our most important lines of defense against bacterial invaders is mucus. The slimy substance coats the inside of the mouth, nose, eyelids, and digestive tract, to name just a few places, creating a barrier to the outside world. Mucus is also home to phages, viruses that infect and kill bacteria. They can be found wherever bacteria reside, but Jeremy Barr and his colleagues noticed that there were even more phages in mucus than in mucus-free areas just millimeters away. The saliva surrounding human gums, for example, had about five phages to every bacterial cell, while the ratio at the mucosal surface of the gum itself was closer to 40 to 1. The researchers found that the phages are studded with antibody-like molecules that grab onto the sugar chains in mucins. This keeps the phages in the mucus, where they have access to bacteria, and suggests that the viruses and the mucus-producing tissue have adapted to be compatible with each other.