Archive for February, 2016

Structural and molecular basis for Ebola virus neutralization by protective human antibodies

27 February, 2016

Ebola virus causes hemorrhagic fever with a high mortality rate and for which there is no approved therapy. Two human monoclonal antibodies, mAb100 and mAb114, in combination, protect nonhuman primates against all signs of Ebola virus disease, including viremia. Here, we demonstrate that mAb100 recognizes the base of the Ebola virus glycoprotein (GP) trimer, occludes access to the cathepsin-cleavage loop, and prevents the proteolytic cleavage of GP that is required for virus entry. We show that mAb114 interacts with the glycan cap and inner chalice of GP, remains associated following proteolytic removal of the glycan cap, and inhibits binding of cleaved GP to its receptor. These results define the basis of neutralization for two protective antibodies and may facilitate development of therapies and vaccines.

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Why is it that structural / molecular immunologic studies always "may facilitate development of therapies and vaccines"?  Really??  How about looking at what the actual vaccines did in terms of eliciting sterilising immunity, or controlling viral load?

So nice work, but it characterises the mode of action of just two monoclonal antibodies from the spectrum of many thousand that would be involved in reaction to infection, and of the hundreds that are involved in vaccine responses, and the many in any single individual that would be involved in actual neutralisation of infectivity / ADCC / infected cell killing, etc.

What I’m getting at is that whole protein responses, in the context of live vaccine vector inoculations, are almost certainly more complex than anything that involves just these two antibodies, and elegant immunological / structural studies are a minor part of understanding the whole problem.

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GM viruses could help prevent animal diseases jumping to humans

23 February, 2016

Vaccinating wildlife with genetically-modified viruses could one day help stop diseases like Ebola and MERS jumping from animals to humans, researchers say.

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In principle, a great idea – BUT, as was pointed out, using live viruses in an effectively uncontrolled manner COULD result in all sort of unforeseen outcomes.

Like making a killer virus that drastically reduces numbers of a given species, like myxomatosis and RHDV did to rabbits [OK, they were supposed to].

Like making a virus that spreads to NON-target animals, and does…what?  Start a zombie plague?  Mutate to virulence, and cause havoc?

The point is, WE DON’T KNOW what may happen – and in circumstances like that, it may be safer to leave well alone!

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+strand RNA viruses stimulate host phosphatidylcholine synthesis at viral replication sites

22 February, 2016

Positive-strand RNA viruses [(+)RNA viruses] include many important human, animal, and plant pathogens. A highly conserved and indispensable feature of (+)RNA virus infection is that these viruses proliferate and reorganize host membranes to assemble viral replication complexes (VRCs). We show that brome mosaic virus (BMV) stimulates phosphatidylcholine (PC) synthesis at the viral replication sites. BMV recruits a host enzyme involved in PC synthesis to support proper VRC formation and genomic replication. We further show that hepatitis C virus and poliovirus also promote accumulation of PC at the viral replication sites, revealing a feature common to a group of (+)RNA viruses. This virus-specific step can be targeted to develop a broad-spectrum antiviral strategy with the least side effects on host growth.


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This is a big deal: it demonstrates a common requirement among very different (+)strand RNA viruses – picornaviruses, flaviviruses and bromoviruses – for the same lipid – phosphatidylcholine (PC) – and makes the point that inhibiting PC synthesis significantly inhibits viral replication.  That means the same therapy could be used for viruses that are otherwise so different as to have no obvious similarity at all, other than genome polarity.  Great stuff!

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World hunger: what the Ebola virus can teach us about saving crops

19 February, 2016

Rapid genetic disease screening will be the key to saving East Africa’s crops – just as it was during West Africa’s ebola crisis.

When the deadly Ebola virus struck West Africa last year, one thing that became clear was that the region lacked access to quick diagnostic toolsthat could help identify those infected and help contain the virus’s spread.

As the world swung into action to combat the emergency, one crucial factor that helped to curb the epidemic was the arrival of backpacks containing portable genetic sequencing computers – a technology not readily available in the affected countries.

What has that story got to do with world hunger, beyond the fact that both hunger and disease are featured in the United Nations’ Sustainable Development Goals?

If we can bring the same technologies to bear against crop diseases as well as human ones, we can help eradicate hunger – a less newsworthy and more slow-burning problem than Ebola, but far more deadly in terms of the human toll.

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Interesting insight – because in 2007, some of the same folk who wrote this were involved in two workshops that I attended, in Bellagio and in Zanzibar, on setting up a plant disease diagnostic network for Africa.  We had folk from the Rockefeller Foundation there, Gates Foundation too, and we did a lot of good work – to no end, because the proposal did not fly.

Their points are highly valid: I have pointed out elsewhere, and others too, that plant diseases can kill people just as human diseases can.  Indirectly, maybe, and due to lack of food caused by plant pathogens, but taking a deadly toll nonetheless (see here:

The sad fact is that there is next to nothing in place in most of Africa for the kinds of molecular diagnostics that folk working with human diseases take for granted.  Oh, there are a few centres in the more sophisticated African countries where ELISA kits can be used, and places like Uganda, Kenya and even Malawi have labs and dedicated people – but these are the exceptions, and the overall picture is dismal.

What we need are comprehensive surveys of crops across Africa, in all of the breadbasket countries that supply most of the maize, cassava, sweet potatoes and the like, and of vegetable-growing areas in all countries, to see what is there.

Once that is known, then surveillance programmes could be set up, to monitor outbreaks of dangerous diseases, insect vector populations and their role in spreading plant disease – and provide information to assess real and potential crop losses.

All it would take is money – and some of the kit that came to Africa for the Ebola outbreak in West Africa recently.  We even have a plan that could be dusted off – and a good Africa-wide network to help make it happen.

Oh, and some political will, and some planning.  That’s the difficult bit….

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The scientific journey of AIDS from despair to cautious hope

18 February, 2016

Despite the breakthroughs in HIV and AIDS research, without an effective vaccine, the world will not get to zero new infections and deaths.

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Nice series of articles – I covered the first one earlier.

HIV/AIDS for many of has been a long and sustained learning experience that has paralleled the pandemic: it has provided numerous invaluable insights into the workings of the human immune system, into how retroviruses work, how they evolve – and how to treat the diseases HIV infection leads to, as well as how to develop therapies for those infected.

I hope we are past the midpoint of the pandemic curve now: as a young academic, I remember the first reports of AIDS the syndrome, the discovery of the viruses involved.

As an old academic who has been involved in research on candidate vaccines against it, I am still hoping that we will conquer the virus in my lifetime.

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Mimivirus – making us think again about virus classification

13 February, 2016

This article – by one of the discoverers of Mimivirus – argues that the new giant DNA viruses are different from other viruses and that as a result, we neew to create a new brach of microbes. Other virologists are more cautious, suggesting that Mimivirus can fit within the current scheme of virus taxonomy. Either…

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I don’t think that The Big Lads justify a new domain of life: while they may be the largest monophyletic group of viruses with the most ancient provenance, they are not the ONLY monophyletic group.  A good case could be made for caudoviruses (Order Caudovirales) too; the ss(+)RNA viruses are also probably ancient and have a variety of origins – so there is nothing special about Mimi and her cousins, other than they are (so far) the most complex viruses in terms of genome size and encoded content.

They are still most certainly viruses, by all of the best accepted definitions (including mine B-), in that they are still obligate intracellular parasites that do not have a translational apparatus, and which cause particles to be assembled to transport their genomes.

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Your next DNA vaccine might come from tobacco

12 February, 2016

We don’t have much practice at this sort of thing, but seeing as we just got something REALLY cool published, and the man who largely made it possible is now a science writer, we decided to ask him to write a press release.  So he did.  Thanks, Paul Kennedy – take a bow, twice!

“In a pioneering step towards using plants to produce vaccines against cervical cancer and other viruses, University of Cape Town (UCT) researchers have generated synthetic human papillomavirus- derived viral particles called pseudovirions in tobacco plants.

“We’ve succeeded in making a completely mammalian viral particle in a plant – proteins, DNA, everything. That’s enormously exciting,” says Dr Inga Hitzeroth of the Biopharming Research Unit (BRU) at UCT.Dr_Inga_Hitzeroth

In an Open Access study just published in Nature Scientific Reports, BRU researchers report using tobacco plants to create a synthetic viral particle known as a pseudovirion.

A pseudovirion looks like a virus, but it contains no infectious viral DNA. A virus is usually made up of a shell surrounding the virus’s own genetic material. Pseudovirions instead carry whatever DNA the researcher wishes to include within the shell of proteins that make up the outer coating of the virus.

Until now, such particles have only ever been created in yeast or mammalian cell cultures – this is the first time researchers have successfully created pseudovirions in plants.

The BRU is part of a new movement known as biopharming, which means using plants as biological factories. Biopharming has been used to create flu vaccines, potential Ebola drugs, and an enzyme used to treat Gaucher’s Disease in humans. The technique employs the cellular machinery within tobacco plants or other plant cells to manufacture enzymes, antibodies or even the viral capsid proteins (the proteins that make up the shell of a virus), which act as vaccines.

In this research, the BRU has taken biopharming one step further by using plants to create a viral shell that encloses ‘custom’ DNA selected by researchers. “What’s unique here is that DNA that was manufactured within the tobacco plant is now being incorporated into a viral particle to form a pseudovirion,” says Hitzeroth.

The shell of this pseudovirion was that of human papillomavirus (HPV) type 16, the virus responsible for over 50% of cervical cancer cases worldwide.

The BRU team hope this new plant-based technology could one day be used to test future HPV vaccines. First author of the study, Dr Renate Lamprecht, renateexplains: “We need pseudovirions to test any new HPV vaccine candidates. At the moment it is very expensive to make pseudovirions – we need to make them in mammalian cell culture, it needs to be sterile, and the reagents are very expensive.”

All these factors contribute to the high cost of current HPV vaccines, which are actually virus-like particles. Virus-like particles (VLPs) are similar to pseudovirions, but they contain no DNA. Plant- made pseudovirions, as demonstrated by this study, could reduce the cost of testing and manufacturing such vaccines, thus helping to make HPV vaccines affordable where they are needed most: the developing world.


Plant-made HPV pseudovirions containing geminivirus-derived DNA

The BRU team compared these new plant-made pseudovirions against the more widely-used mammalian cell culture-produced particles by using what’s known as a neutralisation assay. In this test (which is commonly used to test new HPV vaccine candidates), cells are ‘infected’ with pseudovirions, with or without pre-treatment with neutralising antibodies. The DNA inside the pseudovirion carries a ‘reporter gene’ that produces a protein that can give off a light signal. Thus, an infectious pseudovirion gets into the cell and gives off light, but one that is stopped by neutralising antibodies does not.

“I was jumping up and down the first time I saw the neutralisation results, but I repeated the experiment a few times to be sure, asking myself, ‘is everything correct, are all the controls there?’” explains Lamprecht. “It was a very exciting moment for us when we confirmed that neutralisation had occurred.”

Right now, every laboratory makes pseudovirions for such neutralisation experiments themselves. Dr Hitzeroth hopes that one day, they won’t have to: “we’re in the initial stages, but if we optimise the process and get the yield much higher, we think it’s a product that could be sold all over the world.”

ed ebola

Ed’s Ebola shirt

For Professor Ed Rybicki, Director of the BRU, this achievement was enormously satisfying, as it brought together two strands of his research interests that have co-existed for over 20 years.

“Seventeen years ago, I had the idea to combine making HPV VLPs in plants with a DNA plant virus we were working on, to see if we could make pseudovirions. It took until now for the technology to finally come together, but it shows what can happen in biotechnology if you’re willing to persevere.”

The BRU are also hoping to use this technology to create a therapeutic vaccine, which would also be a first of its kind. The idea would be to use the pseudovirion to deliver DNA that could treat an ongoing HPV infection or even a tumour.

With global acceptance and support for the biopharming movement growing rapidly, it might not be too long before the first plant-produced HPV vaccine is making a difference in Africa and around the world.”

For further enquiries, contact Dr Hitzeroth. For more info on biopharming, check out this Q&A session from Sense About Science.

Why Africa can’t afford to have an outbreak of the Zika virus

10 February, 2016

With limited laboratory capacity and a lack of experts and funding, an outbreak of the Zika virus in Africa could be problematic.

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Yeah…sure.  It could be Bad.


BUT: as South African epidemiologists have pointed out, it’ll only be a problem IF the mosquito that transmits it elsewhere, comes here – because our local A aegypti doesn’t have the same behaviour, and will vastly outnumber and possibly outcompete any import variety.


And it’s endemic in tropical Africa – meaning many people are immune already.


So scaremongering about Zika in Africa is possibly a little irresponsible – unless it’s being used as a stalking horse for an agenda for setting up continent-wide arbovirus surveillance, or spurring on efforts to set up an African CDC.  Which I would heartily endorse.


The stuff about lack of reagents is spot-on: which is why we have a proposal in the works to provide just such, using plants to it.  Watch this space….

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Zika: a realistic view of what we know

2 February, 2016

“As you’ve probably seen, unless you’ve been living in a cave, Zika virus is the infectious disease topic du jour. From an obscure virus to the newest scare, interest in the virus has skyrocketed just in the past few weeks:   I have a few pieces already on Zika, so I won’t repeat myself here.…”

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Nice, cautious piece by Tara Smith.  I have been trying, via Twitter, to damp some of the hysteria and hype about Zika – but who cares about one cautious voice?  So there should be MORE – and this is one such.

Zika virus is a flavirirus related to dengue and yellow fever and Japanese encephalitis and West Nile viruses, and like them, is mosquito-transmitted.  In fact, it is transmitted by the same “yellow fever mosquito” – Aedes aegypti – as transmits YFV and dengue, and like them, has been spread around the tropics of the planet along with the mosquito vector.

The mosquito is an interesting beast, because it is hardy, can breed in very small deposits of water, such as are found in urban areas in flower vases, uncovered barrels, buckets and such, likes preying on humans, and flies during the day – unlike most of its relatives.  It also has a penchant for breeding in places like discarded car tyres, and it turns out that a LOT of these are literally shipped around the developing world from developed countries like Japan and the USA, which has resulted in the mosquito going worldwide from its African origins.

The Zika virus is nothing like as nasty as dengue or YFV or JEV: there are apparently no deaths of children or adults that can be attributed to infection with it, unlike the case with its relatives.  Where it is potentially dangerous is the apparent linkage – in naive populations – with microcephaly, and also a stronger link with the paralytic Guillain-Barre syndrome.

I stress “in naive populations”: the virus was discovered in Uganda’s Zika Forest in 1947, and is endemic over large swathes of tropical Africa, where it is not associated with anything other than mild and often inapparent infections, easily confused with influenza.  Its endemicity also means that literally everyone that can be infected will have been AS A CHILD – and presuming that like YFV, exposure leads to lifelong immunity, adults will be immune to the virus AND the purported side effects.  It is interesting that the African subspecies of A aegypti – which has apparently NOT left Africa – does not like to bite humans and is probably a less efficient vector.

What will probably happen in Brazil and the South, Central and North American countries that it has spread to or is in the process of doing so, is that it will become endemic there – especially if it adapts to being spread by other mosquitoes such as the much more common Culex spp., which may have already happened.  When that happens, the African experience will become the norm – and hopefully the hype and hysteria will die away.

Until then – well, a vaccine would be nice!  It may help that one of the best characterised and safest attenuated vaccines known is the 17D strain of the genetically similar yellow fever virus – and that unlike dengue, there are no distinct or non-cross-protecting strains or types of Zika virus, meaning only one vaccine should be necessary. And a simple thing to do would be to replace one or both of the membrane proteins of 17D with the Zika equivalents.  Remember who told you…B-)

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