Archive for the ‘Uncategorized’ Category

Resurrecting Smallpox? Easier Than You Think

17 October, 2014

The virus’s genome is already online. You just need the right lab.

Source: www.nytimes.com

Weeeeeellll…yes and no. Smallpox is a BIIIIG genome – not far off in size to the bacterial genome famously resynthesised by Craig Venter et al., a while ago.  This means it would be a huge undertaking, cost a LOT of money, and need sophisticated facilities to do it.

Not something your average cave-dwelling fanatic could do, then!

States could do it, however: a well-funded lab in even a country like North Korea could theoretically resynthesise a poxvirus – but why bother??  We have vaccines against smallpox right now; growing poxviruses and vaccinia virus in particular is a well-established biotechnology still.

SO I think this is an artificial concern, to be honest. 

See on Scoop.itVirology News

What Would Happen if You Got Ebola?

13 August, 2014

A secondary infection in the U.S. is highly unlikely. But here’s how the healthcare system would respond if there was one.

Source: www.theatlantic.com

Goes without saying that this would happen in a lot of other places, too.  Including our very own South Africa – where it HAS happened, with Marburg, Ebola and Lujo viruses.  Written about right here on ViroBlogy.

See on Scoop.itVirology News

How can geminiviral Rep capture the cell cycle of differentiated plant cells?

12 August, 2014

African cassava mosaic virus (ACMV) in the geminivirus family has being affected 500 million people worldwide by devastating cassava crops during the past decades. It has caused severe symptoms and reduced yield up to the complete loss of roots, the main starchy food source especially for subsistence farmers in Africa. How can a tiny virus with a small genome evoke such dramatic effects? The viral key component, the replication-initiator protein (Rep), forces differentiated plant cells in the phloem to reactivate DNA synthesis. Even more, it does the same in model cells of fission yeast. We have identified, now, a potential cyclin interaction motif, RXL, in the sequence of ACMV Rep, which may be important for cell cycle control. This motif is essential to induce rereplication in yeast and necessary for viral infection of plants.

 

Source: www.virologyhighlights.com

I am a sucker for geminiviruses and their replication – as can be seen in the pages published here and elsewhere over the years.  It is fascinating to me that a small protein like Rep – only ~30 kDa – can do so many things, and especially interfere in such a fundamental way with organised, differentiated cells.

What is even more interesting is that it can do it in such a wide variety of systems: it’s been shown that ACMV can replicate in maize protoplasts as well as in the dicotyledonous cassava; it can evidently function well in yeast as well – and via a pathway that no-one suspected before now.

Truly, a protein of many parts!  Congratulations to Katharina Hipp and to my old friends Bruno and Holger.

See on Scoop.itVirology News

2013 in review: ViroBlogy seems to be doing OK??

5 August, 2014

The WordPress.com stats helper monkeys prepared a 2013 annual report for this blog.

Here’s an excerpt:

The concert hall at the Sydney Opera House holds 2,700 people. This blog was viewed about 24,000 times in 2013. If it were a concert at Sydney Opera House, it would take about 9 sold-out performances for that many people to see it.

Click here to see the complete report.

Has the Time Come to Test Experimental Ebola Vaccines?

30 July, 2014

The Ebola Virus is Spreading Across West Africa in The Largest Outbreak To Date

Mortality rates are currently at 60%, where normally up to 90% of affected people die. Unfortunately, there are no cures or vaccines for the disease, despite its emergence in 1976.

In March of this year, cases of Ebola were reported for the first time in Guinea, Western Africa. Notably, these outbreaks took place in Guinean districts that bordered Sierra Leone and Liberia. In the past, outbreaks have taken place in remote areas of Africa, but this outbreak has had the opportunity to cross border and spread throughout Western Africa, and it has done just that. Now fourth months since the March outbreak, 1,093 people have been infected and there have been a reported 660 deaths attributed to the deadly virus (source: CNN vital signs.)

 

Source: www.vaccinenation.org

I would say – yes!  I am sure the beleaguered healthcare workers in Guinea, Liberia, Sierra Leone and now Nigeria would welcome the experimental vaccine candidates, and the experimental therapeutics, for that matter.

See on Scoop.itVirology News

Internet archaeology

28 June, 2014

There I was, innocently doing a search on

Search the BIONET methods/bionet.molbio.methds-reagnts

- because my own “Manual of Online Molecular Biology Methods” links to it, and I was a regular there when it was operational – when I typed my own name in (as one does), and discovered that I had written this, as an answer to a post of 21 years ago.  Can’t even remember doing it.

 

S Poidinger writes:
> Gimme a K...Gimme an I....Gimme a T....whatdoesitspell?

- and I am prompted to reply:

Well, come on all of you bright young men
ProBoehAmPharm needs your help again
Got itself in a bit of a jam -
Stock price falling in the US of Am
So put down your books, pick up a kit
Gonna do a whole lot of sh*t...

And it's 1, 2, 3
What are we working for
Don't ask me, I don't give a sh*t
Long's I can use a kit

And it's 5, 6, 7
Open up the Plastic box
Ain't no cause to wonder why
ProBoehAmPharm ain't gonna die....

- With apologies to Country Joe and the Fish

Virus experiments risk unleashing global pandemic, study warns

21 May, 2014

See on Scoop.itVirology News

Benefits of scientific testing in the area are outweighed by risks of pathogenic strains spreading round world, say researchers

Ed Rybicki‘s insight:

…and others say "Rubbish!"  I particularly like this bit:

 

"[Ron] Fouchier said…the authors had misinterpreted published data to arrive at their risk of someone picking up a virus in the laboratory. "The truth is that scientific research has never triggered a virus pandemic.""

The report goes on to say:

"Lipsitch and Galvani point out that a flu strain that spread around the world from 1977 to 2009 was probably released in a laboratory accident."

Yes.  But.  That was from the old Soviet Union – and they had a number of nasty things escape from laboratories, including anthrax and weaponised smallpox, by all accounts.

 

See on www.theguardian.com

An ACTUAL killer virus that could rise from the grave

1 May, 2014
Section through Variola virus.  Copyright Russell Kightley Media

Section through Variola virus. Copyright Russell Kightley Media

Having poo-pooed the possibility of killer viruses roaring out of the tundra to kill as all – see here – I find myself having to reconsider my words.  Just slightly, mind, but a reconsideration nonetheless.

This is because of an excellent post in Nature News recently, entitled “Infectious diseases: Smallpox watch“, by Sara Reardon.  This has raised quite a stir in the Twittersphere, as people speculate on just how likely this is, but I think the article itself does a very good job of discussing the possibility that smallpox could come back from the grave(s).

I have discussed smallpox a number of times in this blog, with one of the most read posts being this one by my PhD student (and now postdoc) Alta van Zyl.  I recall a while back a discussion around just how likely it was that people working on expanding what was the Rietfontein Infectious Diseases Hospital (now Sizwe Hospital)’s premises in Johannesburg, would find live smallpox in coffins of people who died of it at the old Hospital and were buried nearby.

The verdict then was “No” – Johannesburg is too hot, and the was seen to be NO chance of the virus surviving the rapid putrefaction that occurs in these parts.

Sara Reardon’s essay, however, raises the real, if rather remote, prospect of there being live smallpox in mummified corpses which have either dried out at low temperatures, or been frozen soon after death, in permafrost.  She says that

“A more likely source of infectious virus would be frozen bodies. Influenza viruses seem to be able to survive freezing in lakes and may thereby infect migrating birds…”

Now the good thing is that people have actually gone out looking for live virus in just such potential sources, and found nothing except fragments of DNA.

However, she also says:

“Another concern is that smallpox could escape from a secret cache. Few biosecurity specialists believe that the two stocks kept at the CDC and VECTOR are the only ones in existence. For instance, variola could very well be in the freezer of someone who defected from the Soviet Union…”

Now, the old Soviet Union had an active programme on weaponising smallpox, with some sources claiming than “several tonnes” of material were eventually made.  There is even evidence that smallpox escaped from a facility in Aralsk, Kazakhstan, in 1971.   What is not so clear is where any of this material is NOW, and in what state it is.

Time to work on the emergency-response smallpox vaccines and strategies, folks – even if you use the potential threat of monkeypox as the reason!

 

 

The Assembly Pathway of an Icosahedral Single-Stranded RNA Virus Depends on the Strength of Inter-Subunit Attractions

27 March, 2014

See on Scoop.itVirology News

The strength of attraction between capsid proteins (CPs) of cowpea chlorotic mottle virus (CCMV) is controlled by the solution pH. Additionally, the strength of attraction between CP and the single-stranded RNA viral genome is controlled by ionic strength. By exploiting these properties, we are able to control and monitor the in vitro co-assembly of CCMV CP and single-stranded RNA as a function of the strength of CP–CP and CP–RNA attractions. Using the techniques of velocity sedimentation and electron microscopy, we find that the successful assembly of nuclease-resistant virus-like particles (VLPs) depends delicately on the strength of CP–CP attraction relative to CP–RNA attraction. If the attractions are too weak, the capsid cannot form; if they are too strong, the assembly suffers from kinetic traps. Separating the process into two steps—by first turning on CP–RNA attraction and then turning on CP–CP attraction—allows for the assembly of well-formed VLPs under a wide range of attraction strengths. These observations establish a protocol for the efficient in vitro assembly of CCMV VLPs and suggest potential strategies that the virus may employ in vivo.

 

Ed Rybicki‘s insight:

I do love it when a paper is published that could have been done pretty much any time in the last 40 years – and with one of my favourite viruses, that I played with a LOT back there before 1980.

Ultracentrifugation, pH meters, ionic strength determinations, EM…all tried and true, and used 40+ years ago. OK, they also used cloned BMV RNA 1 cDNA, and did 3-D image reconstruction from EMs, but hey, they needn’t have done that!  Nice, straightforward physicochemical studies, on a well-characterised virus, with good, simple conclusions. 

Namely, that assembly of the virus is NOT just a simple mix-CP-and-RNA-and-it-will-happen, but that it depends upon both pH, for modulating ionic interactions,and ionic strength for modulating ionic interactions AND the "hydrophobic effect", as we used to know it.

While their conclusions are relevant for assembly of heat- and nuclease-resistant nano particles in vitro, I wonder if they are physiologically relevant: if "correct" assembly depends upon first, turning on CP-RNA attraction (ionic strength shift), and second, turning on CP-CP attraction (pH shift) – where in the cell does that happen?

In their own words, "It is generally accepted that the cytoplasm of plant cells is maintained near neutral pH with ionic strength of approximately 0.1 M. Our in vitro results show that these conditions are insufficient for nucleocapsid formation in the absence of cellular host factors."

Yeeee-ee-eesssss…precisely. What happens in the cell? The answer could lie in the one thing they don’t report, but that some of the heroes of my distant youth – people like JB Bancroft and Thom Hohn, both quoted (from 1970 and 1969 respectively) in this paper, DID do. Namely, investigate what happens at different CP and RNA concentrations, at constant pH and ionic strength.

You see, it was shown 30+ years ago – and I have been lecturing on it since then – that CP and RNA for viruses like BMV / CCMV and MS2 form different complexes with their cognate partners at different molecular ratios. That is, at low CP:RNA ratios, a high-affinity complex is formed, which is basically a ribonucleoprotein complex without structure. Increasing the CP:RNA ratio for both MS2 and CCMV, as I recall (maybe Dick Verduin was involved with CCMV), results in further lower-affinity association of CP with both RNA and already-bound CP – which acts as a nucleation complex – to result in full capsid assembly.

I note that the process in both cases was shown to be specific, for low CP:RNA ratios: that is, it was cognate CP and RNA doing the high affinity nucleation complex formation.

And these guys deliberately used a heterologous RNA…albeit one from a related virus, but still: what would have happened if they’d used CCMV RNA?

Still – great paper, taking me back to when I wrote an essay on "Assembly of Spherical Plant Viruses" in my Honours year in 1977, quoting quite a few of the same references these folk did. Ah, simpler times…B-)

See on www.sciencedirect.com

This Old PI….

7 March, 2014

See on Scoop.itVirology News

Ed Rybicki‘s insight:

I blame Chris Upton


Follow

Get every new post delivered to your Inbox.

Join 578 other followers