Posts Tagged ‘virology’ Virology News

11 February, 2012

This is just to announce that I will be regularly posting “Virology News” updates on a new site I have just set up – as well as occasionally updating another site – “Virology and Bioinformatics from” – which is curated by Chris Upton, of Univ Victoria in Canada.

Even more ways to get your daily viral fix…B-)

A Short History of the Discovery of Viruses – Part 2

7 February, 2012

The Chicken or the Egg?

Possibly the next most important development in virology was the proof that embryonated or fertilized hen’s eggs could be used to culture a variety of important animal and human viruses.  Ernest Goodpasture, working at Vanderbilt University in the USA, showed in 1931 that it was possible to grow fowlpox virus – a relative of smallpox – by inoculating the chorioallantoic membrane of eggs, and incubating them further.

eggWhile tissue culture had in fact been practiced for some time – for example, as early as the 1900s, investigators had grown “vaccine virus” or the smallpox vaccine now called vaccinia virus in minced up chicken embryos suspended in chicken serum – this technique represented a far cheaper and much more “scalable” technique for growing pox- and other suitable viruses.

The Official Discovery of Influenza Virus

Also in 1931, Robert Shope in the USA managed to recreate swine influenza by intranasal administration of filtered secretions from infected pigs.  Moreover, he showed that the classic severe disease required co-inoculation with a bacterium – Haemophilus influenza suis – originally thought to be the only agent.  He also pointed out the similarities between the swine disease and the Spanish Flu, where most patients died of secondary infections.  However, he also suggested that the virus survived seasonally in a cycle involving the pig, lungworms, and the earthworm, which is now known to be completely wrong.

Influenza viruses in pigs

Influenza viruses in pigs

Patrick Laidlaw and William Dunkin, working in the UK at the National Institute for Medical Research (NIMR), had by 1929 successfully characterised the agent of canine distemper – a relative of measles, mumps and distemper morbilliviruses – as a virus, proved it infected dogs and ferrets, and in 1931 got a vaccine into production that protected dogs.  This was made from chemically inactivated filtered tissue extract from infected animals.  Their work built on and completely eclipsed earlier findings, such as those of Henri Carré in France in 1905, who first claimed to have shown it was a filterable agent, and Vittorio Puntoni, who first made a vaccine in Italy from virus-infected brain tissue inactivated with formalin in 1923.

Influenza and Ferrets: the Early Days

Continuing from Laidlaw and Dunkin’s work in the same institute, Christopher Andrewes, Laidlaw and W Smith reported in 1933 that they had isolated a virus from humans infected with influenza from an epidemic then raging.  They had done this by infecting ferrets with filtered extracts from infected humans – after the fortuitous observation that ferrets could apparently catch influenza from infected investigators!  The “ferret model” was very valuable – see here for modern use of ferrets – as strains of influenza virus could be clinically distinguished from one another.

Eggs and Flu and Yellow Fever

Influenza virus and eggs: large-scale culture

Frank Macfarlane Burnet from Australia visited the NIMR in the early 1930s, and learned a number of techniques he used to great effect later on.  Principal among these was the technique of embryonated egg culture of viruses – which he took back to Melbourne, and applied to the infectious laryngotracheitis virus of chickens in 1936.  This is a herpesvirus, first cultivated by JR Beach in the USA in 1932: Burnet used it to demonstrate that it was possible to do “pock assays” on chorioallantoic membranes that were very similar to the plaque assays done for bacteriophages, with which he was also very familiar.  Also in 1936, Burnet started a series of experiments on culturing human influenza virus in eggs: he quickly showed that it was possible to do pock assays for influenza virus, and that

“It can probably be claimed that, excluding the bacteriophages, egg passage influenza virus can be titrated with greater accuracy than any other virus.”

Max Theiler and colleagues in the USA took advantage of the new method of egg culture to adapt the French strain of yellow fever virus (YFV) he had grown in mouse brains to being grown in chick embryos, and showed that he could attenuate the already weakened strain even further – but it remained “neurovirulent”, as it caused encephalitis or brain inflammation in monkeys.  He then adapted the first YFV characterised – the Asibi strain, from Ghana in 1927 – to being grown in minced chicken embryos lacking a spinal cord and brain, and showed in 1937 that after more than 89 passages, the virus was no longer “neurotrophic”, and did not cause encephalitis.   The new 17D strain of YFV was successfully tested in clinical trials in Brazil in 1938 under the auspices of the Rockefeller Foundation, which has supported YFV work since the 1920s.  The strain remains in use today, and is still made in eggs.

Putting a Spin on it: the Ultracentrifuge

A technical development that was to greatly advance the study of viruses was begun in 1923, but only reached fruition by the 1930s: this was the , invented and developed first by in Sweden as a purely analytical tool, and later by and  in the USA as an .  The ultracentrifuge revolutionised first, the physical analysis of proteins in solution, and second, the , by centrifugation at high speeds.

A technical development that was to greatly advance the study of viruses was begun in 1923, but only reached fruition by the 1930s: this was the ultracentrifuge, invented and developed first by Theodor (“The”) Svedberg in Sweden as a purely analytical tool, and later by JW Beams and EG Pickels  in the USA as an analytical and preparative tool.  The ultracentrifuge revolutionised first, the physical analysis of proteins in solution, and second, the purification of proteins, viruses and cell components, by centrifugation at high speeds.

Analytical centrifugation and calculation of molecular weights of particles gave some of the first firm evidence that certain proteins, and virus particles, were large, regular objects.  Indeed, it came to be taken as a given that one of the fundamental properties of a virus particle was its sedimentation coefficient, measured in svedbergs (a unit of 10-13 seconds, shown as S20,W).  This is also how ribosomes of bacteria and eukaryotes came to be named: these are known as 70S (prokaryote) and 80S ribosomes, respectively, based on their different sedimentation rates.

Purifying Viruses

Given that the nature of viruses had prompted people to think of them as “chemical matter”, researchers had attempted from early days to isolate, purify and characterise the infectious agents.  An early achievement was the purification of a poxvirus in 1922 by FO MacCallum and EH Oppenheimer.  CG Vinson and AM Petre, working with the infectious agent causing mosaic disease in tobacco – tobacco mosaic virus, or TMV – showed in 1931 that they could precipitate the virus from suspension as if it were an enzyme, and that infectivity of the precipitated preparation was preserved.  Indeed, in their words: “…it is probable that the virus which we have investigated reacted as a chemical substance”.

Viruses in Crystal

An important set of discoveries started in 1935, when Wendell Stanley in the USA published the first proof that the infectious agent causing mosaic disease in tobacco – tobacco mosaic virus, or TMV – could be crystallised, at the time the most stringent way of purifying molecules.  He also reported that the “protein crystals” were contaminated with small amounts of phosphorus.  An important finding too, using physical techniques, was that the TMV “protein” had a very high molecular weight, and was in fact composed of large, regular particles.  This was a very significant discovery, as it indicated that some viruses at least really were very simple infectious agents indeed.

TMV particle: 95% protein, 5% RNA

However, his conclusion that TMV was composed only of protein was soon challenged, when Norman Pirie and Frederick Bawden working in the UK showed in 1937 that ribonucleic acid (RNA) – which consists of ribose sugar molecules linked by phosphate groups – could be isolated consistently from crystallised TMV as well as from a number of other plant viruses, which accounted for the phosphorus “contamination”.  This resulted in the realisation that TMV and other plant virus particles – now known to be virions – were in fact nucleoproteins, or protein associated with nucleic acid.

Seeing is Believing: the Electron Microscope

First Electron Microscope with Resolving Power Higher than that of a Light Microscope. Ernst Ruska, Berlin 1933 Wikipedia CC BY-SA 3.0,

First Electron Microscope with Resolving Power Higher than that of a Light Microscope. Ernst Ruska, Berlin 1933
Wikipedia CC BY-SA 3.0,

The development of the electron microscope, in Germany in the 1930s, represented a revolution in the investigation of virus structures: while virions of viruses like variola and vaccinia could just about be seen by light microscopy – and had been, as early as 1887 by John Buist and others – most viruses were far too small to be visualised in this way. 

While Ernst Ruska received a Nobel Prize in 1986 for developing the electron microscope, it was his brother Helmut who first imaged virus particles – using beams of electrons deflected off virus particles coated in heavy metal atoms.  From 1938 through the early 1940s, using his “supermicroscope”, he imaged virions of poxviruses, TMV, varicella-zoster herpesvirus, and bacteriophages, and showed that they were all particulate – that is, they consisted of regular and sometimes complex particles, and were often very different from one another.  He even proposed in 1943 a system of viral classification on the basis of their perceived structure.

While electron microscopy was also used medically to some extent thereafter – for example, in differentiating smallpox from chickenpox by imaging particles of variola virus and varicella-zoster virus, respectively, derived from patients’ vesicles – its use was limited by the expense and cumbersome nature of sample preparation.  This all changed from 1959 onwards, when Sydney Brenner and Robert Horne published “A negative staining method for high resolution electron microscopy of viruses”.  This method involves the use of viruses in liquid samples deposited on carbon-coated metal grids, and then stained with heavy-metal salts such as phosphotungstic acid (PTA) or uranyl acetate

This simple technique revolutionised the field of electron microscopy, and within just a few years much information was acquired about the architecture of virus particles. Not only were the overall shapes of particles revealed, but also the details of the symmetrical arrangement of their components. Some beautiful examples can be seen here, at the Cold Spring Harbor site.

Click here for Part 3: Animal Cell Culture

and here for Part 1: Introduction

Copyright February 2012 by EP Rybicki and Russell Kightley, unless otherwise specified.

Rating blogs for assessment purposes

12 August, 2011

Seeing as I was talking with colleagues in the world outside Virology (yes, I do have them) (yes, there is one!) about how one could get assessed in the academic environment for activities like blogging, it was quite heartening to get an email from one Tracy Myers, about this blog featuring in the “’s list of the Top 50 Blogs about Biology“.

Not in the top 5, I discover, but hey, top 50 in a big class is OK…B-)

But we are distracted from the theme: how does one get material such as I produce in this blog, assessed in the obsessively publication metric-conscious University environment?

With difficulty, it would appear: AJC, I would like your opinion on this!  Access stats are one way, and I have used WordPress’s rather nice summary table for access over the life of this blog to demonstrate that (1) people do actually get to it, and in quite significant numbers, (2) they come from all over the world.  And I would especially like to thank our Saudi Arabian Virology student readers at this juncture!

It’s something the powers-that-be at Unis are going to have to get their heads around – because it’s an increasing trend for academics to blog, and for their students to read said blogs, and to be influenced (hopefully positively) by them.

But I’ll just cherish my badge for a while…B-)  Thanks Tracy!

Best Blog Badge

On the utility of Pink Floyd’s “The Grand Vizier’s Garden Party” as a metaphor for virus multiplication

16 September, 2010

…which pretty much explains the concept…what’s that?  Why?  Well, because the above-mentioned song – off the very strange and very wonderful album Ummagumma, released in 1969 – incorporates three subsections.

From the tracklisting:

“The Grand Vizier’s Garden Party” (N Mason) – 8:44

  • Part 1: “Entrance” – 1:00
  • Part 2: “Entertainment” – 7:06
  • Part 3: “Exit” – 0:38

All clear now?  No?  Ah, well, you need to consult the relevant parts of the Web material, don’t you?  Which would be here, and here…and of course, we never got around to exit as such, so you may as well look here instead.

Which just goes to show that, however hard one tries, it is close to impossible to update a whole set of Web pages AND keep all the links current!  Ah, well – that’s an aspect of electronic teaching with its own comment, right here.

But I digress: “metaphor”, I said.  Something like a “simile”, only different, as I’ve heard it described.  And another digression, to cartoon country this time – which shows how we virologists normally treat metaphors and their filthy ilk.

And is it a good metaphor, you ask?  Well, yes – for one reason, because

  • first, students still know who Pink Floyd is/are, so they remember it better;
  • second, because it is a very simple encapsulation of the process;
  • third, because it neatly separates three crucial aspects of the virus life cycle -
  • and fourth, it gives you the opportunity to describe three very different kinds of strategy for messing with said life cycle.

And thinking of 4, and just of HIV for example, those would be:

  • entry inhibitors, like antibodies or fusion inhibitors
  • nucleoside analogue or non-nucleoside reverse transcriptase inhibitors, and
  • protease inhibitors to prevent polyprotein processing.

And I’ve been doing it for 25 years, and see no reason why I should stop using it now.  Or stop playing “Another Brick in the Wall” when I put up long definitions.   Or stop mentioning that Pink Floyd have the second-longest song title of which I am aware.  Or that Hoagy Carmichael* has the longest….

Enough said, probably.  Just to say that it helps make virology fun.  At least for me  B-)

* = I’m a Cranky Old Yank in a Clanky Old Tank on the Streets of Yokohama with my Honolulu Mama Doin’ Those Beat-o, Beat-o Flat-On-My-Seat-o, Hirohito Blues

MicrobiologyBytes Archive

14 December, 2007

Before I established this site, I posted a number of guest blogs to do with viruses on Alan Cann’s very wonderful MicrobiologyBytes site. Here are links to all the virus-related ones.

Maybe Not Quite The End

Posted on January 15, 2008
Review of a paper describing the receptor for the H5N1 HA protein

Given the current scare over H5N1 influenza virus in swans in the UK, it is possibly timely to recall that I wrote a little while ago in MicrobiologyBytes about how easy it appeared to be for […]

Bandicoot Blues

Posted on November 30, 2007
Description of a unique newly-described virus that looks like a chimaera of a papillomavirus and a polyomavirus

Now that the dust has begun to settle after the launch of Merck’s much-hyped Gardasil genital papillomavirus vaccine – discussed in MicrobiologyBytes here and here – people are turning again to looking at the natural history […]

Hurting rather than helping?

Posted on November 21, 2007
Some news on the failure of the Merck Adenovirus 5-vectored HIV vaccine

It should not have escaped the eye of the interested bystander that there has been a most unfortunate and premature end to a HIV vaccine trial recently – and that something that had been tested as […]

A Deeper Meaning

Posted on November 10, 2007
Some microbiology-related poetry….

I inadvertently became a published literary critic a little while ago. A long-time English Department colleague asked me for some help interpreting the collected works of possibly the most important modern poet from South Africa, and […]

Don’t look now, they’re in your genes

Posted on September 14, 2007
Description of natural insertions of virus gene fragments into a variety of organisms and how they elicit pathogen-derived resistance

And they’re protecting you! If you’re an insect, that is. Or possibly a plant.
In a remarkable convergence of news, an Israeli group led by Ilan Sela described how Israeli acute paralysis virus, which is implicated in […]

To bee or not to bee

Posted on September 11, 2007
News of how a single virus is suspected in the causation of “colony collapse disorder” of bee hives in the USA

A major recent mystery in US agriculture has been the phenomenon of “colony collapse disorder” (CCD) in honey bees. […]

This is the End

Posted on August 29, 2007
H5N1 highly pathogenic avian influenza virus mutates…

This is the End. Or the beginning of the end. Or possibly, the end of the beginning?
To misquote the immortal Bill Shankly: “It’s not a matter of life and death: it’s much more important than that”.
Having […]

Rolling down the road

Posted on August 27, 2007
Musings on rolling circle replication in viruses

In my idle moments (alas, too few these days!) I often try to think up lists of rock songs with a virus theme: you know, like “Cucumo” by the Beech Boys… “I got them ol’ burnin’, […]

Rooting the tree

Posted on August 3, 2007
News on inferring “ancestor sequences” for HIV to help make broadly effective vaccines

While fossilized viruses have never been found, we can often infer probable lines of evolutionary descent by analysis of extant genomic sequences. This sort of molecular phylogenetic approach has thrown up all sorts of interesting […]

It’s Life, Jim, but not as we know it…

Posted on July 24, 2007
Exploring what it means to be “alive”

Which could well apply to viruses, my very own favourite organisms – after all, they don’t respire, grow, excrete or any of those other good things […]

A feeling for the molechism*

Posted on June 26, 2007
Musings on what viruses are.

I think it’s permissible, after working on your favourite virus for over 20 years, to develop some sort of feeling for it: you know, the kind of insight that isn’t […]

Plus ça change, plus c’est … le same Web, only better?

Posted on June 8, 2007
A personal history of teaching Virology via the Web.

My, how things do change… I found myself reflecting, while I was looking over the detritus on our Web server of some 13 years of posting pages on the Web. “Orphan” pages, unconnected […]

ViroBlogy: blogging with a virological bias

21 November, 2007

This is intended to be a weblog for informing people – and especially students in the Department of Molecular and Cell Biology at the University of Cape Town - about news of interesting developments in the general area of Virology as a discipline.

I – Ed Rybicki - will be updating this site on a regular basis, especially during term time.  It WILL form part of the curriculum…B-)  There will also be a teaching Wiki for student collaborative learning (watch this space).


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