Archive for November, 2010

Farewell, Frank Fenner!

23 November, 2010

While visiting the Australian National University in Canberra recently, I noticed in the lobby outside their Club dining room, a most interesting tapestry.  Interesting, because it looked like a colourised electron micrograph (it depicts myxomavirus), and because it had a plaque beneath it commemorating their own Professor Frank Fenner.  I was familiar with him because he authored an extremely useful book – Medical Virology – which I had used for educating myself and for teaching; I was also aware that he was an extremely eminent poxvirologist who had been active in the field for decades – and was still working despite having retired in 1979.

Variola virus, the agent of smallpox. Image courtesy Russell Kightley Media.

And then today I heard that he had died this week, at the age of 95.

Virology is still a young field, as I discover while trying to research its history for my sabbatical project: the concept dates only from 1898; only a couple of generations of scientists have been active in this field since it started – and Frank Fenner probably overlapped with nearly all of them.  He was born in 1914, which meant he was in at the morning of virology as we know it, while many of the first practitioners were still around – and he stayed active until very recently, when the science had changed almost out of all recognition.  He will be missed.

I am sharing this message that was sent out by the Director of the John Curtin School of Medical Research at ANU, where Fenner worked as an Emeritus Professor, as it is probably the best short account of his life.

“It is with great sadness that I communicate to you the passing of Professor Frank Fenner.

Frank John Fenner AC, CMG, MBE, FRS, FAA (born 21 December 1914, died 22 November 2010) was an Australian scientist with a distinguished career in the field of virology. His two greatest achievements are cited as overseeing the eradication of smallpox during his term as Chairman of the Global Commission for the Certification of Smallpox Eradication, and the control of Australia’s rabbit plague through the introduction of myxoma virus.

Professor Fenner was Director of the John Curtin School from 1967 to 1973. During this time he was also Chairman of the Global Commission for the Certification of Smallpox Eradication. In 1973 Professor Fenner was appointed to set up the new Centre for Resource and Environmental Studies at the Australian National University (ANU). He held the position of Director until 1979.

Professor Fenner has been elected a fellow of numerous faculties and academies, including Foundation Fellow of the Australian Academy of Science (1954), Fellow of the Royal Society (1958), and Foreign Associate of the United States National Academy of Sciences (1977). During his career Professor Fenner received many awards. Among these are the Britannica Australia Award for Medicine (1967), the Australia and New Zealand Association for the Advancement of Science Medal (1980), the World Health Organization Medal (1988), the Japan Prize (1988), the Senior Australian Achiever of the Year (1999), the Albert Einstein World Award for Science (2000), and the Prime Minister’s Science Prize (2002).

A man of decisive scientific action and strong opinions, Professor Fenner’s last interview with The Australian is extremely thought provoking and can be found here:

A summary of Frank’s remarkable career can be found here:

The last public recognition of Professor Frank Fenner’s accomplishments occurred here at JCSMR during the First International Meeting on Translational Medicine earlier this month: On 1 November 2010 Professor Fenner received a standing ovation by world leaders in academic medicine during the opening of the Conference and on 2 November 2010 he was recognized by the Conference as he and Sir Gus Nossal stood by their portraits, which hang side by side at the National Portrait Gallery. A picture of Professor Fenner at JCSMR taken on 1 November 2010 next to Gus Nossal is attached.

Further notices will be sent with information regarding Professor Fenner as plans to honor his accomplishments evolve.

With best regards,


Professor Julio Licinio
Director John Curtin School of Medical Research
The Australian National University
Canberra, ACT 2601, Australia ”

Thanks to Bertram Jacobs of ASU for sharing this with me.

Ed Rybicki

Integrating the enemy

23 November, 2010

Ever since I first discovered them as a student, sometime in 1976, I have found retroviruses fascinating.  Not quite as fascinating as Ebola, possibly, but captivating nonetheless.  The whole concept of a virus that converts a perfectly ordinary mRNA into dsDNA, then  inserts it into the host chromosome as a provirus in a eukaryotic version of lysogeny – was truly wonderful.

And as the years have gone by, I have seen no reason to lessen the feeling of wonderment: other

The Retroid Virus Replication Cycle

viruses – now called pararetroviruses, including both hepadnaviruses and plant viruses – whose replication  starts at a different position in the  cycle have been found; these and retroviruses have been integrated into a whole family of “reverse transcribing elements” – retrons – which include prokaryote transposons; HIV burst in on the scene, and suddenly we know so much about how the immune system works, because a virus messes with it so well.

But the actual mechanics of one particular process have consistently escaped elucidation – until now.  The 11 November issue of Nature contains, apart from only the second SF short-short story by a South African (kudos, Anand!), a Letter of great interest.

The mechanism of retroviral integration from X-ray structures of its key intermediates
Goedele N. Maertens, Stephen Hare & Peter Cherepanov
Nature 468,326–329 (11 November 2010) doi:10.1038/nature09517

To establish productive infection, a retrovirus must insert a DNA replica of its genome into host cell chromosomal DNA. This process is operated by the intasome, a nucleoprotein complex composed of an integrase tetramer (IN) assembled on the viral DNA ends. The intasome engages chromosomal DNA within a target capture complex to carry out strand transfer, irreversibly joining the viral and cellular DNA molecules. Although several intasome/transpososome structures from the DDE(D) recombinase superfamily have been reported, the mechanics of target DNA capture and strand transfer by these enzymes remained unclear. Here we report crystal structures of the intasome from prototype foamy virus in complex with target DNA, elucidating the pre-integration target DNA capture and post-catalytic strand transfer intermediates of the retroviral integration process. [my emphasis - Ed] The cleft between IN dimers within the intasome accommodates chromosomal DNA in a severely bent conformation, allowing widely spaced IN active sites to access the scissile phosphodiester bonds. Our results resolve the structural basis for retroviral DNA integration and provide a framework for the design of INs with altered target sequences.

Basically, these folk have managed to freeze-frame several different stages of the process in crystals, by clever use of synthetic DNA targets – and then solved the structures.  NOT trivial, and the pictures are absolutely superb.  So are the movies…but you need to subscribe to Nature to see those.

Harking back to a previous post – Entrance, Entertainment and Exit, anyone? -  the more we know about viruses, the more we can mess with them.  And this is a VERY good step along that road.

The largest marine virus yet

13 November, 2010

This is another welcome guest post from Gillian de Villiers, a Scientific Officer in our Vaccine Group.  This was presented as a Journal Club article recently, and fit so well into my continuing theme of “viral diversity from water” that I asked her to write it up.  Thanks Gillian!

Giant virus with a remarkable complement of genes infects marine zooplankton

Matthias G. Fischer, Michael J. Allen, William H. Wilson, and Curtis A. Suttle

PNAS published ahead of print October 25 2010

This publication covers the sequencing of the genome of Cafeteria roenbergensis virus(CroV).  This nucleocytoplasmic large DNA virus (NCLDV) is the largest marine virus described to date, and its closest relative is Acanthamoeba polyphaga Mimivirus.

Among the questions raised in this paper are:

  • what is the evolutionary origin of big viruses?
  • Did they get their genes from horizontal gene transfer (including from eukaryotes), or
  • are the “eukaryotic” genes viral in origin?

Spoiler alert: the authors do not answer this question.

Please note: this is a virus from a seawater host.  It is the largest marine virus yet found, but how hard has anyone been looking?  This ties in with Ed’s theme that we should be looking for viral diversity and interesting things in the water, because interesting things have been found there.

Some background…

This lytic virus strain was isolated off the coast of Texas in the 1990s.  The host, Cafeteria roenbergensis was originally misidentified as a Bodo species.  It is a major micro flagellate grazer (microzooplanton = major ocean predator) a 2-6um “bicoecid heterokant phagotrophic flagellate” and has been found in multiple marine environments including surface waters, deep sea sediment and hydrothermal vents.

In other words, the host is an extremely significant part of the ocean ecosystem, and has been found in most places.  The authors note that protists host the largest viruses known and that other giant viruses probably are widespread in the oceans, but so far only the Acanthamoeba-infecting giant viruses have been characterised (Acanthamoeba does not live in the ocean). Viral infections of cyanobacteria play a significant role in global oxygen production; in a similar way the viral infections by CroV may have implications for carbon and other nutrient cycling and the “food chain” in the oceans, although this is beyond the scope of the article.]


The genome is the second-largest viral genome described and at 730kb is very AT rich.  Approximately 618kb is thought to be coding with 544 predicted protein-coding genes.  At least 274 genes are expressed during infection.  22 percent of CroV CDSs (coding sequences) were probably best related to eukaryotic genes.  Most CroV CDSs had unknown function, but 32% of CDSs could be assigned a putative function.

For enzymatic functions that have not previously been reported in any other viruses you can refer to Table S1 of the Supplemental materials.

This is similar to CroV’s closest known relative, Mimivirus, where of 911 predicted genes only 300 were assigned a predicted function (see table).  Only 1/3 of their genes are common to these two viruses!  This suggests tremendous diversity within the nucleocytoplasmic large DNA viruses, as they may have common evolutionary origins for some genes, but not for others.  As viruses are not monophyletic (although the NCLDVs may be) and can be considered to be bags of protein that contain genetic material and share a strategy (rather than an origin) this may not be particularly surprising.  But I find it amazing that so many potential genes, and so many unique potential genes, have been found in these organisms.

Included in the genes assigned function are genes involved in translation.  CroV encodes an isoleucyl-tRNA synthetase and putative homologs of eukaryotic translation initiation factors.  22 tRNA genes and two putative tRNA-modifying enzymes: tRNA pseudouridine 5S synthase and tRNAIle lysidine synthetase were found.  Mimivirus also has four tRNA synthetases and several putative translation factors.

Cafeteria roenbergensis virus Acanthamoeba polyphaga Mimivirus
~730kb dsDNA genome ~1200kb dsDNA genome
300nm capsid 500-750nm capsid (publications differ)
Largest marine virus yet described Largest virus yet described
Second-largest virus yet described -
544 predicted genes 911 predicted genes
174 genes with predicted function 300 genes with predicted function
Host: Cafeteria roenbergensis Host: Acanthamoeba castellani (amoeba)
Habitat: marine environment Habitat: soil (?freshwater)
Genes shared with Mimivirus ~ 1/3 Genes shared with CroV ~ 1/5

Similarly to other large DNA viruses a number of DNA repair genes were found.  This includes a base excision repair pathway that appears complete.  In addition crov115’s gene product is predicted to be a CPD class 1 photolyase, the first viral homologue in its class.  Crov149 appears to be part of a recently described photolyase/cytochrome group found in several bacterial phyla and euryarchaeotes, but not among established types of photolyase.  The authors suggest that the only eukaryote with this gene, Paramecium tetraurelia may have acquired it by horizontal gene transfer from a giant virus

CroV also has transcription-related genes including eight DNA-dependent RNA polymerase II subunits, six transcription factors involved in transcription initiation, elongation, and termination, a tri-functional mRNA capping enzyme, a poly (A) polymerase, as well as helicases.  Mimivirus provides considerably more genes for protein transcription and translation than most viruses, and sets up its own ‘virus factory’ in the cytoplasm of the cell.  It is possible that CroV has a similar strategy, with viral gene transcription independent of the host and occurring in the cytoplasm.

Of the three DNA topoisomerases, two are very similar to the counterparts in Mimivirus.  CroV TopoIB is the first viral homolog of the eukaryotic subfamily, but the Mimivirus TopoIB appears to be from the bacterial group.  Although the evolutionary origin appears to differ, the topoisomerases are presumably important in transcription, translation or packaging of giant virus genomes, as they appear in both CroV and Mimivirus genomes.

CroV has four inteins: self-splicing proteins.  They are found in DNA-dependent DNA polymerase B (PolB), TopoIIA, DNA-dependent RNA polymerase II subunit 2 (RPB2) and the large subunit of ribonucleotide reductase (RNR).  Inteins have previously been found in viruses infecting eukaryotes, including Mimivirus PolB.  CroV TopoIIA intein is the first case of an intein in a DNA topoisomerase gene.

Microarray analysis on the 12-18 hr infection cycle showed around half the predicted genes, and 63% of the tested genes were expressed during infection.  Work on Mimivirus and PBSC-1 showed transcription of nearly all predicted genes, so this work may underestimate the true transcriptional activity of CroV.  CroV gene expression has an early phase 0-3 hrs after infection affecting 150 genes, and a late phase affecting 124 genes 6 hrs or later post-infection including all the structural components predicted.  A conserved early promoter motif “AAAAATTGA” was identified in 35% of CDSs and is nearly identical to the Mimivirus early promoter motif “AAAATTGA”.  A promoter element for genes transcribed during the late phase of CroV infection was found that is unrelated to the putative late promoter motif in Mimivirus.

A genomic fragment involved in carbohydrate metabolism was also found.  This 38kb fragment includes enzymes for biosynthesis of 3-deoxy-D-manno-octulosonate (KDO).  This is part of the lipopolysaccharide layer in gram-negative bacteria and is found in the green alga Chlorella and the cell wall of higher plants. Ten of the enzymes involved in carbohydrate metabolism were expressed, suggesting a role in viral glycoprotein biosynthesis, suggesting the virion surface may be coated with KDO- or sialic acid-like glycoconjugates. 

There are no homologs in Mimivirus suggesting this region must have been acquired after the CroV and Mimivirus lineages split (or that the Mimivirus lineage lost it subsequently?).  This may have been acquired from bacteria, however GC content is even lower than for the rest of the CroV genome, and a number of the proteins are phylogenetically between bacterial and eukaryotic homologs.

Phylogenetics and Speculations

Phylogenetic reconstruction of NCLDV members. Redrawn and simplified from Fig. 4. The unrooted Bayesian Inference tree was generated from a 263-aa alignment of conserved regions of DNA polymerase B

CroV is an addition to the group of NCLDVs including Ascoviridae, Asfarviridae, Iridoviridae, Mimiviridae, Phycodnaviridae, Poxviridae and Marseillevirus, which are presumed to be monophyletic. CroV seems to be the closest known relative to Mimivirus although it is substantially smaller.  The topology of the NCLDV tree strongly suggests the five largest viral genomes (all mimiviruses) are more closely related to each other than to other NCLDV families.  They may have originated from an ancestral virus that was already an NCLDV that encoded more than 150 proteins.

Mimivirus is the most studied NCLDV, and is the largest.  Most Mimivirus genes have no cellular homologs and may be very ancient, with 1/3 of genes having originated through gene and genome duplication and less than 15% of the genes having potentially been acquired by horizontal gene transfer from eukaryotes and bacteria.  The CroV genome analysis is consistent with this view of giant virus evolution, with gene duplication and lineage-specific expansion contributing to the size of the CroV genome.  The 38kb carbohydrate metabolism fragment may be a potential case of large-scale horizontal gene transfer from a bacterium.  The PolB gene of CroV has high similarity with those of other marine isolates so it may represent a major group of marine viruses, that despite being virtually unknown have ecological significance.

CroV again shows overlap between large viruses and cellular life forms, adding to questions about the evolutionary history of giant viruses as well as what life itself is.

Prions: infectious states of protein folding

6 November, 2010

In my teaching of virology, I have always covered “virus-like entities” as well – which includes satellite viruses, plasmids, viroids, satellite nucleic acids – and prions.  Pronounced PREE-ONS, according to Stanley Prusiner, the man who got a Nobel Prize in 1997 for describing them, who told me this in a bus in 1987 coming back from an especially well lubricated International Congress of Virology dinner in Edmonton, Alberta.

So it may or may not have been remembered as well as it could have been.  Especially as I vaguely recall singing him and Ted Diener – of viroid fame – a song about salesmen, and getting 25c in my hat for my trouble.

In any case, the inclusion of prions as being virus-like is based more on their ability to cause disease, and be infectious, than on their similarity to viruses – because there really is no similarity at all.

Consider: viruses are obligate intracellular parasites, which use particles assembled inside cells to transport their nucleic acid genomes around in order to establish new infections.  Satellite viruses – of which there are both DNA and RNA varieties – are the same, except for needing some functions provided in trans by an autonomous virus.  Satellite nucleic acids – again, both RNA and DNA – require a helper virus and do not encode their own coat proteins, and sometimes encode no protein at all.  Viroids are single-strand circular RNAs which effectively code for nothing but their own secondary and tertiary structures, which in turn serve to co-opt the host RNA pol II – a transcription polymerase – to replicate their genomes via a rolling-circle mechanism.  And sometimes also encode “ribozyme” enzyme functions, such as ligase/RNAse.

Prions, on the other hand, are proteins encoded for and made by normal cells – only eukaryotes as far as we know – which have suffered a structural conversion or misfolding into a state which allows them to act as templates for the structural conversion of normally folded proteins of the same or similar sequence.  Moreover, the way in which the aberrant folding occurs – to a variety of related but distinct structures – may define the type of disease and its manifestation.

In other words, prions are nothing more or less than “an infectious state of protein folding which leads to pathology“.

Transmission of BSE prions to humans. Copyright Russell Kightley Media

I have done a number of pieces on prions over the last couple of years, largely due to the morbid curiosity engendered by the Great British Beef Scandal of years gone by, when it was shown that meat from a significant number of cattle suffering from bovine spongiform encephalopathy or BSE, aka Mad Cow Disease, had entered the human food chain in the UK – and several other places.  What resulted was a fatal infectious disease, known as new variant Creutzfeld-Jakob disease (vCJD) to distinguish it from the classical (largely sporadic, or genetic) CJD.  There was a well-justified fear at the time that vCJD cases would reach epidemic proportions – but this has not happened, and the number of cases reached a quite low peak and has been decreasing for some time.

I have covered prions again today because of a ProMED post I have just received, which covers the present state of human prion diseases very nicely, and which I reproduce below.



ProMED-mail post <>

ProMED-mail is a program of the International Society for Infectious Diseases <>

[With the continuing decline of the number of cases in the human  population of variant Creutzfeldt-Jakob disease -- abbreviated  previously as vCJD or CJD (new var.) in ProMED-mail -- it has been  decided to broaden the scope of the occasional ProMED-mail updates to  include other prion-related diseases. In addition to vCJD, data on  other forms of CJD: sporadic, iatrogenic, familial, and GSS  (Gerstmann-Straussler-Scheinker disease) are included also since they  may have some relevance to the incidence and etiology of vCJD. - Mod.CP]

In this update:

[1] UK: National CJD Surveillance Unit – monthly statistics as of Mon  1 Nov 2010 – no new vCJD cases

[2] France: Institut de Veille Sanitaire – monthly statistics as of  Fri 29 Oct 2010 – no new vCJD cases

[3] USA: National Prion Disease Pathology Surveillance Center – data  not updated since 31 Jul 2010, no indigenous vCJD

[4] Prion disease susceptibility  ******

[1] UK: National CJD Surveillance Unit – monthly statistics as of Mon  1 Nov 2010 – no new vCJD cases

Date: Mon 1 Nov 2010

Source: UK National CJD Surveillance Unit, monthly statistics [edited] <>

The number of deaths due to definite or probable vCJD cases remains  170. A total of 4 definite/probable patients are still alive so the  total number of definite or probable vCJD cases remains 174.  Although 3 new deaths due to vCJD were recorded in 2009 and now 3  deaths in 2010 so far, the overall picture is still consistent with  the view that the vCJD outbreak in the UK is in decline, albeit now  with a pronounced tail. The 1st cases were observed in 1995, and the  peak number of deaths was 28 in the year 2000, followed by 20 in  2001, 17 in 2002, 18 in 2003, 9 in 2004, 5 in 2005, 5 in 2006, 5 in  2007, one in 2008, 3 in 2009, and now 3 so far in 2010.  Totals for all types of CJD cases in the UK so far in the year 2010

——————————————————————- During the 1st 10 months of 2010, there have been 126 referrals, 54  fatal cases of sporadic CJD, 3 fatal cases of vCJD, 2 cases of  iatrogenic CJD, 2 cases of familial CJD, and one case of GSS.

– Communicated by: ProMED-mail <>  ******

[2] France: Institut de Veille Sanitaire – monthly statistics as of  Fri 29 Oct 2010 – no new vCJD cases

Date: Fri 5 Nov 2010

Source: IVS – Maladie de Creutzfeldt-Jakob et maladies apparentees [in French, trans. & summ. Mod.CP, edited] <>

During the 1st 10 months of 2010, there were 1332 referrals, 75  confirmed cases of sporadic CJD, 4 cases of familial CJD, and no  cases of iatrogenic CJD or vCJD.  A total of 25 cases of confirmed or probable vCJD have been recorded  in France since records began in 1992. There was 1 case in 1996, 1 in  2000, 1 in 2001, 3 in 2002, 2 in 2004, 6 in 2005, 6 in 2006, 3 in  2007, 2 in 2009, and none so far in 2010.  The 25 confirmed cases comprise 13 females and 12 males. All 25 are  now deceased. Their median age is 37 (between 19 and 58). 7 were  resident in the Ile-de-France and 18 in the provinces. All the  identified cases have been Met-Met homozygotes. No risk factor has  been identified. One of the 25 had made frequent visits to the United  Kingdom, during about 10 years from 1987.

– Communicated by: ProMED-mail <>  ******

[3] USA: National Prion Disease Pathology Surveillance Center – data  not updated since 31 Jul 2010, no indigenous vCJD

Date: Fri 5 Nov 2010

Source: US National Prion Disease Pathology Surveillance Center [edited] <>

No update since 31 Jul 2010.  During the 7 month period 1 Jan 2010 to 31 Jul 2010, there were 204  referrals, 124 of whom were classified as prion disease, comprising  85 cases of sporadic CJD, 20 of familial CJD, and no cases of  iatrogenic CJD or vCJD.  — Communicated by: ProMED-mail <>  ******

[4] Prion disease susceptibility

Date: Mon 1 Nov 2010

Source: Proceedings of the National Academy of Sciences of the USA  (PNAS) [edited] <>

Ref: MQ Khan, B Sweeting, VK Mulligan, et al: Prion disease  susceptibility is affected by beta-structure folding propensity and  local side-chain interactions in PrP. Proc Natl Acad Sci USA 2010  (Epub ahead of print); doi:10.1073/pnas.1005267107

———————————————————————- Abstract ——–

Prion diseases occur when the normally alpha-helical prion protein  (PrP) converts to a pathological beta-structured state with prion  infectivity (PrPSc). Exposure to PrPSc from other mammals can  catalyze this conversion. Evidence from experimental and accidental  transmission of prions suggests that mammals vary in their prion  disease susceptibility: hamsters and mice show relatively high  susceptibility, whereas rabbits, horses, and dogs show low susceptibility.  Using a novel approach to quantify conformational states of PrP by  circular dichroism (CD), we find that prion susceptibility tracks  with the intrinsic propensity of mammalian PrP to convert from the  native, alpha-helical state to a cytotoxic beta-structured state,  which exists in a monomer-octamer equilibrium. It has been  controversial whether beta-structured monomers exist at acidic pH;  sedimentation equilibrium and dual-wavelength CD evidence is  presented for an equilibrium between a beta-structured monomer and  octamer in some acidic pH conditions.  Our X-ray crystallographic structure of rabbit PrP has identified a  key helix-capping motif implicated in the low prion disease  susceptibility of rabbits. Removal of this capping motif increases  the beta-structure folding propensity of rabbit PrP to match that of  PrP from mouse, a species more susceptible to prion disease.  –[my emphasis]

Communicated by: ProMED-mail <>

[This research provides a physical explanation of how changes in the  structure of the prion protein can affect the prion disease  susceptibility of different mammals. - Mod.CP]

This last comment is especially interesting, because it highlights something that has been of interest for some time – as in, how do prions from one species affect another?  In other words, just how transmissible are prion diseases, and in which directions?  And which variants of the gene predispose towards greater or lesser susceptibility?

Food for serious thought, undoubtedly.  But I’m still a meat eater….

Rinderpest: gone, but not forgotten – yet.

5 November, 2010

Rinderpest virus infects cattle, buffalo and several species of antelope among other animals: it is a member of the genus Morbillivirus,family Paramyxoviridae, and is related to measles and mumps viruses in humans, distemper virus in dogs, and a variety of relatively newly-described viruses in marine mammals.  It also almost certainly gave rise to measles virus sometime around the 11th-12th centuries CE, as an originally zoonotic infection – sourced in domestic animals – took root in humans and began to be passed around (see MicrobiologyBytes).

Electron micrograph of a morbillivirus particle showing the membrane, matrix, and inner helical nucleocapsid. Image by LM Stannard

The ICTVdB generic description of morbilliviruses is as follows:

Virions consist of an envelope and a nucleocapsid. Virus capsid is enveloped. Virions are spherical to pleomorphic; filamentous and other forms are common. Virions measure (60-)150-250(-300) nm in diameter; 1000-10000 nm in length. Surface projections are distinctive spikes of haemagglutinin (H) and fusion (F) glycoproteins covering evenly the surface. Surface projections are 9-15 nm long; spaced 7-10 nm apart. Capsid/nucleocapsid is elongated with helical symmetry. The nucleocapsid is filamentous with a length of 600-800(-1000) nm and a width of 18 nm. Pitch of helix is 5.5 nm.

The Mr of the genome constitutes 0.5% of the virion by weight. The genome is not segmented and contains a single molecule of linear negative-sense, single-stranded RNA. Virions may also contain occasionally a positive sense single-stranded copy of the genome (thus, partial self-annealing of extracted RNA may occur). The complete genome is 15200-15900 nucleotides long.

Wikipedia describes rinderpest virus as “…an infectious viral disease of cattle, domestic buffalo, and some species of wildlife. The disease was characterized by fever, oral erosions, diarrhea, lymphoid necrosis, and high mortality.”   And: “The term Rinderpest is taken from German, and means cattle-plague.”

The Food and Agriculture Organisation (FAO) has a Division of Animal Production and Health: their web site details a campaign known as the Global Rinderpest Eradication Programme (GREP), which has been going since 1994.

With very little fanfare, I might point out: as a practicing teaching virologist, I was totally unaware of it.  Anyway: they state that:

Rinderpest has been a dreaded cattle disease for millennia, causing massive losses to livestock and wildlife on three continents. This deadly cattle plague triggered several famines and caused the loss of draught animal power in agricultural communities in the 18th, 19th and 20th centuries.

…which is a little of an understatement: Wikipedia tells us that

“Cattle plagues recurred throughout history, often accompanying wars and military campaigns. They hit Europe especially hard in the 18th century, with three long pandemics which, although varying in intensity and duration from region to region, took place in the periods of 1709–1720, 1742–1760, and 1768–1786. There was a major outbreak covering the whole of Britain in 1865/66.”

“Later in history, an outbreak in the 1890s killed 80 to 90 percent of all cattle in Southern Africa, as well as in the Horn of Africa [and resulted in the deaths of many thousands of people who depended on them]. Sir Arnold Theiler was instrumental in developing a vaccine that curbed the epidemic. [my insert / emphasis] More recently, a rinderpest outbreak that raged across much of Africa in 1982–1984 cost at least an estimated US$500 million in stock losses”.

When commenting on the significance of the achievement, John Anderson, the head of the FAO, described GREP’s announcement that Rinderpest had been eradicated as:

The biggest achievement of veterinary history“.

The 19th century southern African outbreak was devastating enough that people still remember it as a legendary time of hardship – and then there was the 1980s outbreak.  Another South African interest in rinderpest is that the legendary Sir Arnold Theiler had a hand in making a vaccine: he did this around the turn of the 20th century, by simultaneously injecting animals with blood from an infected animal and antiserum from a recovered animal: this protected animals for long enough to allow their immune systems to respond to the virus – but was rather risky, even though it was used for several decades.

In the 1920s J. T. Edwards in what is now the Indian Veterinary Research Institute serially passaged the virus in goats: after 600 passages it no longer caused disease, but elicited lifelong immunity. However, it could still cause disease in immunosuppressed cattle.

In 1962, Walter Plowright and R.D. Ferris used tissue culture to develop a live-attenuated vaccine grown in calf kidney cells.  Virus that had been passaged 90 times conferred immunity without disease even in immunosuppressed cattle, was stable, and did not spread between animals.  This vaccine was the one that allowed the prospect of eradicating the virus, and earned Plowright a World Food Prize in 1999.

But a memory may be all rinderpest is any more – as the GREP site says the following:

“The last known rinderpest outbreak in the world was reported in 2001 (Kenya). Based on the above-mentioned investigations, FAO is confident that all rinderpest virus lineages will prove to be extinct.”

This was also announced via the BBC on the 14th October, 2010.  They said:

The eradication of the virus has been described as the biggest achievement in veterinary history and one which will save the lives and livelihoods of millions of the poorest people in the world.

And the significant bit:

If confirmed, rinderpest would become only the second viral disease – after smallpox – to have been eliminated by humans.

Let us reiterate that: only the second viral disease, ever, to have been eliminated.  And how was this possible?  Unlike smallpox, which has only humans as a natural and reservoir host (although it almost certainly also got into us from animals), rinderpest attacked a wider range of hosts.  However, it seemed mainly to have a reservoir in domesticated cattle, and it did not have an arthropod vector; moreover, the vaccine was cheap and effective.

This is momentous news: we may well have succeeded in ridding the planet of what has been a very significant disease of livestock and of wild animals, which has caused untold agricultural loss throughout recorded history, and which has resulted in enormous human hardship as well.  We have also made a natural species go extinct – but it won’t be missed.  Like smallpox, it was completely sequenced some time ago, so we could theoretically recreate it if we ever needed to.

From GREP:

Though the effort to eradicate rinderpest has encountered many obstacles over the past several decades, the disease remains undetected in the field since 2001. As of mid 2010, FAO is confident that the rinderpest virus has been eliminated from Europe, Asia, Middle East, Arabian Peninsula, and Africa. This has been a remarkable achievement for veterinary science, evidence of the commitment of numerous countries, and a victory for the international community.

Amen.  However – it’s not quite time to celebrate as the certification is only planned for 2011.

And now for mumps, and measles too.


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