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Mimivirus unveiled

22 May, 2009

Alan Cann blogged on May 13th 2008 on mimivirus structure, in “Mimivirus and the Stargate“, following publication of a PLoS Biology paper on “Distinct DNA Exit and Packaging Portals in the Virus Acanthamoeba polyphaga mimivirus“ by Abraham Minsky’s group at the Weizman Institute in Israel.  This paper has some stunning EM images and cryoEM reconstructions, which prompt their summary statement:

“…we identified a large tunnel in the Mimivirus capsid that is formed shortly after infection, following a large-scale opening of the capsid [which they term the “stargate”]. The tunnel allows the whole viral genome to exit in a rapid, one-step process. DNA encapsidation is mediated by a transient aperture in the capsid that, we suggest, may promote concomitant entry of multiple segments of the viral DNA molecule.”

Given that PLoS Biology has an Open Access policy which  “…allow[s] anyone to download, reuse, reprint, modify, distribute, and/or copy articles in PLoS journals, so long as the original authors and source are cited”,  I HAVE to share these pictures with you.

 

Mimivirus Stargate

Mimivirus Stargate

(A) TEM image of cryo-fixed sectioned and stained extracellular Mimivirus particles revealing a star-shaped structure at a unique vertex.
(B) Cryo-TEM image of a whole vitrified fiber-less Mimivirus.
(C) SEM image of the star-shaped structure in a mature extracellular Mimivirus particle.
(D) Cryo-SEM of an immature, fiber-less particle.
(E) Tomographic slice of a mature intracellular Mimivirus particle captured at a late (12 h post infection) infection stage.
(F and G) Volume reconstruction of the particle shown in (E), revealing the presence of an outer (red) and inner (orange) capsid shells. The star-shaped structure is present in both shells but adopts partially open (dark, star-like region), and completely sealed configurations in the outer and inner shells, respectively.
(H) Superposition of the two shells in (F) and (G).
Scale bars, 100 nm in (A, B, D, and E), and 200 nm in (C).

Schematic Representation of a Mimivirus Particle at Its Final Uncoating Stage

Zauberman N, Mutsafi Y, Ben Halevy D, Shimoni E, Klein E, et al. (2008) Distinct DNA exit and packaging portals in the virus PLoS Biol 6(5): e114.   doi:10.1371/journal.pbio.0060114

 

Schematic Representation of a Mimivirus Particle at Its Final Uncoating Stage

Schematic Representation of a Mimivirus Particle at Its Final Uncoating Stage

 

The capsid (red) is opened at the stargate, allowing for fusion of the viral and phagosome membranes (light and dark blue, respectively), thus forming a star-shaped membrane conduit.

Zauberman N, Mutsafi Y, Ben Halevy D, Shimoni E, Klein E, et al. (2008) Distinct DNA exit and packaging portals in the virus PLoS Biol 6(5): e114.   doi:10.1371/journal.pbio.0060114

 

 

 I commented at the time of Alan’s blog that:

“It is becoming apparent to me – especially now as I do a 10-year revision of my Web teaching material – that there is a hitherto unsuspected level of complexity in the way big viruses get their genomes into cells – and back out into virions. Phycodnaviruses may emulate phages in dissolving their way through cell walls AND injecting DNA; now mimiviruses have special mechanisms for both loading virions and getting their DNA out.

Watch this space: a major growth area in structural biology and virology.”

And, of course, it has come to pass: Michael Rossmann’s group at Purdue University and their collaborators have just published a paper entitled “Structural Studies of the Giant Mimivirus” , also in PLoS Biology, in which they explore in greater detail aspects of the structure, particularly as this is related to getting DNA out of the particles.

Their paper has the most stunning images and reconstructions, including images which show that the “starfish” shaped portal seems to be detachable – and that the unique stargate-associated 5-fold rotational axis of symmetry also has associated with it a depression in the inner nucleocapsid, which is undoubtedly associated with delivery of the DNA within.

Stargate

(A–C) Surface-shaded rendering of cryoEM reconstruction of untreated Mimivirus. (A) Looking down the starfish-shaped feature associated vertex, (B) looking from one side, and (C) looking from the opposite side of the “starfish”-associated vertex.

(D) The “starfish”-associated vertex was removed to show the internal nucleocapsid with its concave surface facing the special vertex.

(E) Central slice of the reconstruction looking from the side of the particle showing the concave face of the nucleocapsid and the low density space beneath the “starfish”-associated vertex. A perfectly icosahedral particle is outlined in gray to show the extension of the unique vertex.

(F) Central slice of the reconstruction looking along the 5-fold axis from the starfish-shaped feature showing the enveloped nucleocapsid surrounded by a lower density space. The coloring is based on radial distance from the center of the virus. Gray is from 0 to 1,800 Å, red from 1,800 to 2,100 Å, and rainbow coloring from red to blue between 2,100 and 2,500 Å.

The scale bars in all panels represent 1,000 Å.

doi:10.1371/journal.pbio.1000092.g005

This latest paper makes summary comments as follows:

“The enveloped genome within the larger viral capsid, perhaps supported by fibers …, has some similarity to eukaryotic cells. In contrast, the external peptidoglycan component mimics bacterial cell walls …. In addition, the existence of a unique vertex in Mimivirus, possibly for genome delivery …, is reminiscent of tailed bacteriophages. These observations are consistent with other results …, implying that Mimiviruses and some other large icosahedral dsDNA viruses have gathered genes from eukaryotic, prokaryotic, as well as archaeal origins [my emphasis].

The three-dimensional cryoEM reconstruction reported here, which was made possible in part by relaxing the icosahedral symmetry, is of a virus whose volume is an order of magnitude larger than has previously been reported. Thus, the detection of a unique vertex may have been missed in other structural studies in which strict icosahedral symmetry had been imposed [my emphasis].”

There are two important points here – one of which may be wrong.

The first is that mimiviruses et alia “…have gathered genes from eukaryotic, prokaryotic, as well as archaeal origins”: given the evolutionary speculations published by Susan-Monti et al. (Virus Research 117 (2006) 145–155), who say:

“Our current hypothesis is that DNA viruses are of deep evolutionary origin close to the origin of the other domains of life.”,

and point out the virus does not seem to have exchanged much DNA (=horizontal gene transfer) with its host despite a presumably ancient association.  This builds on Suhre et al. (PNAS 102 : 14689-14693, 2005), who say:

“Our bioinformatics and comparative genomics study revealed a unique feature of Mimivirus among the eukaryotic domain [sic]: the presence of a highly conserved AAAATTGA motif in the immediate 5′ upstream region of 50% of its protein-encoding genes. By analogy with the known promoter structures of unicellular eukaryotes, amoebal organisms in particular, we propose that this motif corresponds to a TATA box-like core promoter element. This element, and its conservation, appears to be specific of the Mimivirus lineage and might correspond to an ancestral promoter structure predating the radiation of the eukaryotic kingdoms ….

Mimivirus genes exhibiting this type of promoter might be ancestral as well. [my emphasis].”

Thus, it is possibly more likely that eukaryotes and possibly prokaryotes have garnered genes from mimi- and other viruses, rather than the converse!

The second point, given that they ARE a structural biology group, is much more likely: missing unique non-icosahedral capsid structures because of averaging could mean there is a whole world of specialised machinery in large DNA viruses which has simply been missed up till now.

I reiterate, watch this research space….  Anyone interested in mimivirus basics would also be well advised to look here.

Posted in Evolution, General, Viruses | 6 Comments »

HIV Vaccine Day

19 May, 2009

And as one involved (or formerly involved, thanks to the effective demise of our funding agency…) in HIV vaccine research, it is criminal that I missed this yesterday – but the UCT Monday paper caught it, so let’s see what they said:

First human trial of UCT’s HIV vaccine
18 May 2009

 World AIDS Vaccine Day, May 18, marks the occasion in 1997 when US President Bill Clinton challenged researchers to come up with an AIDS vaccine within the following decade, stating that such a vaccine was the only way to eliminate the threat of AIDS. …

Researchers from UCT’s Institute of Infectious Disease and Molecular Medicine (IIDMM) have announced that their two new preventative HIV vaccines have reached the first stage of human clinical trials, a first for Africa.

This trial, called SAAVI 102/HVTN 073, is also a milestone for South Africa. The country is one of the few developing nations to have developed an HIV vaccine and progressed it into human clinical trials.

Professor Anna-Lise Williamson is leader of the team at the IIDMM.

The Desmond Tutu HIV Centre, based at the IIDMM, is one of three sites in the world that will conduct the trials. The others sites are in Johannesburg and Boston in the US.

These vaccines are a culmination of eight years of research by scientists at the IIDMM, UCT, and collaborators from the US National Institutes of Health and the Vaccine Research Centre. Their development and testing has been underpinned by funding from the South African AIDS Vaccine Initiative (SAAVI) and the US National Institute of Allergy and Infectious Diseases (NIAID).

…The initial human trial is being conducted jointly with the HIV Vaccine Trials Network and the NIAID, part of the US National Institutes of Health.

There is a wealth of science behind the vaccines, of course: I am listing a few of the papers giving the historical background to the DNA and the modified vaccinia Ankara virus (MVA, a smallpox vaccine strain) that are about to be used in the trial, below.

Broad, high-magnitude and multifunctional CD4+ and CD8+ T-cell responses elicited by a DNA and modified vaccinia Ankara vaccine containing human immunodeficiency virus type 1 subtype C genes in baboons.  Burgers WA, Chege GK, Müller TL, van Harmelen JH, Khoury G, Shephard EG, Gray CM, Williamson C, Williamson AL.  J Gen Virol. 2009 Feb;90(Pt 2):468-80.

A multigene HIV type 1 subtype C modified vaccinia Ankara (MVA) vaccine efficiently boosts immune responses to a DNA vaccine in mice.  Shephard E, Burgers WA, Van Harmelen JH, Monroe JE, Greenhalgh T, Williamson C, Williamson AL.  AIDS Res Hum Retroviruses. 2008 Feb;24(2):207-17.

Construction, characterization, and immunogenicity of a multigene modified vaccinia Ankara (MVA) vaccine based on HIV type 1 subtype C.  Burgers WA, Shephard E, Monroe JE, Greenhalgh T, Binder A, Hurter E, Van Harmelen JH, Williamson C, Williamson AL.  AIDS Res Hum Retroviruses. 2008 Feb;24(2):195-206.

Design and preclinical evaluation of a multigene human immunodeficiency virus type 1 subtype C DNA vaccine for clinical trial.  Burgers WA, van Harmelen JH, Shephard E, Adams C, Mgwebi T, Bourn W, Hanke T, Williamson AL, Williamson C.  J Gen Virol. 2006 Feb;87(Pt 2):399-410.

Construction and characterisation of a candidate HIV-1 subtype C DNA vaccine for South Africa.  van Harmelen JH, Shephard E, Thomas R, Hanke T, Williamson AL, Williamson C.  Vaccine. 2003 Oct 1;21(27-30):4380-9.

Characterization and selection of HIV-1 subtype C isolates for use in vaccine development.  Williamson C, Morris L, Maughan MF, Ping LH, Dryga SA, Thomas R, Reap EA, Cilliers T, van Harmelen J, Pascual A, Ramjee G, Gray G, Johnston R, Karim SA, Swanstrom R.  AIDS Res Hum Retroviruses. 2003 Feb;19(2):133-44.

The development of HIV-1 subtype C vaccines for Southern Africa.  Williamson AL.  IUBMB Life. 2002 Apr-May;53(4-5):207-8. Review.

Posted in HIV, Vaccines: General, Viruses | 1 Comment »

Are we there yet??

13 May, 2009

As I sit here in the grip of a rhino/toga/adenovirus infection [yes, acute rhinitis, just recovered from sore throat, feel like cr@p], it is hard to be optimistic about the demise of the Influenza A H1N1 “Mexico Flu” outbreak – but various media are now jumping as enthusiastically onto the “It Was All a False Alarm” bandwagon as they did onto the “We’re All Doomed” train.

Was it a false alarm?

Has the threatened pandemic gone away?

Peter Singer, the director of the McLaughlin-Rotman Centre for Global Health at University Health Network and University of Toronto, wrote this in Canada’s National Post on May 11th [bolded red comments my emphais]:

It’s been a fortnight since global attention began fixating on flu. There have been over 4,379 cases worldwide and more than 280 in Canada. We are likely past the midpoint of this episode and it’s not the “big one.” We learned lessons from SARS that we applied to this flu outbreak. This time, how have we done and what have we learned?

I would give Canadian public health authorities an A grade. …

I would give the global response a B grade. The human flu emergency turned into a mini Mad Cow-type crisis. Calling it “swine flu” initially skewered the international pork trade, even though public health authorities emphasized that you can’t catch flu from eating pork chops. In Egypt, authorities slaughtered pigs owned by a poor Christian minority group, fanning religious conflict. Afghanistan’s only known pig–in the Kabul zoo — has been quarantined. The casual musings of a World Health Organization official, and the outbreak in Alberta pigs, didn’t help.

The World Health Organization response was robust, but its pandemic scale sends the wrong signal to the public. It can reach its top level in a mild pandemic so it appears to foretell doomsday even if people around the world have only the sniffles. Meanwhile, some countries reacted to criticisms of their actions during SARS with questionable quarantines, such as with the group of healthy Quebec students [and Mexicans] quarantined in China.

Well, so far it looks like he agrees with the thesis that the “pandemic” scare was mostly hype.  But he goes on to warn us:

Did we cry wolf ? No. The flu virus is a wolf in sheep’s clothing. Flu, a cunning adversary, can mutate to be more transmissible, lethal and drug resistant. Some have argued the media is drawing attention away from other public health priorities; in fact the flu is probably drawing attention away from Paris Hilton. It is a sad coincidence, though, that while a million people died in the 1957 and 1968 flu pandemics, the same number, mostly children under five in Africa, die each year from malaria.

What is next? This flu episode will probably end like some TV shows: “to be continued.” We’ll be tuning into the flu season just starting in the southern hemisphere and our flu season here next fall.

The threat of flu is constant. It’s like the threat of terrorism. The virus needs to break through only once; we need to stop it every time. But this epidemic of H1N1 has left us better prepared for future pandemics.

So did you all register that?  Possibly, just possibly, the flu outbreak is dying away IN THE NORTHERN HEMISPHERE.  WHERE THE FLU SEASON IS OVER.  JUT IN TIME FOR THE SOUTHERN HEMISPHERE’S SEASON.  And this, we remind you, is followed in October or so by a new northern hemisphere flu season.

Singer finishes with:

In a severe pandemic, most sickness and death will be in the developing world. Unfortunately, the globalization of disease threats is greater than the globalization of health defences. Mexico’s anti-viral stockpile at the beginning of the epidemic was only one million doses for 110 million people [compared to Canada’s 55 million for ~20 million by the end], and there are concerns about future availability of flu vaccine in the developing world. Canada should help because we are compassionate and capable, and because, as this epidemic shows, we are all in this together in an interconnected world.

Amen, brother Singer…so in other words, the developing world epidemic is probably still coming, it will be worse than the outbreak we’ve just seen, and there will be way too few drugs to deal with it.

Posted in Evolution, Influenza viruses, Vaccines: General, Viruses | 2 Comments »

…And the Virus Rolled On….

4 May, 2009

ProMED – that ever-so-reliable source of breaking epidemiological news – gives us this as of yesterday.

From the WHO:

Influenza A(H1N1) – update 11 — 3 May 2009 [abridged]
As of 3 May 2009, 17 countries have officially reported 898 cases of influenza A(H1N1) infection, and 20 deaths.
Mexico has reported 506 confirmed human cases of infection, including 19 deaths. The higher number of cases from Mexico in the past 48 hours reflects ongoing testing of previously collected specimens.
The United States Government has reported 226 laboratory confirmed human cases, including one death.
The following countries have reported laboratory confirmed cases with no deaths:

 

  • Austria (1),
  • Canada (85),
  • Colombia (1),
  • China, Hong Kong Special Administrative Region (1),
  • Costa Rica (1),
  • Denmark (1),
  • El Salvador (2),
  • France (2),
  • Germany (8),
  • Ireland (1),
  • Israel (3),
  • Netherlands (1),
  • New Zealand (4),
  • Republic of Korea (1),
  • Spain (13),
  • Switzerland (1)
  • the United Kingdom (15)

Further information on the situation will be available on the WHO [/CDC] website on a regular basis.

WHO advises no restriction of regular travel or closure of borders.

 It is considered prudent for people who are ill to delay international travel and for people developing symptoms following international travel to seek medical attention, in line with guidance from national authorities.

 
And finally, pigs with the virus: 

Canada on [2 May 2009] reported the identification of the A(H1N1) virus in a swine herd in Alberta. It is highly probable that the pigs were exposed to the virus from a Canadian farm worker recently returned from Mexico, who had exhibited flu-like symptoms and had contact with the pigs.

There is no indication of virus adaptation through transfer from human to pigs at this time.

There is no risk of infection from this virus from consumption of well-cooked pork and pork products. [my bold/red]

 From South Africa’s News24:

 
Swine flu vaccine in the works
29/04/2009 14:01  – (SA)  

 

 Geneva – Four laboratories are at “various stages” of working on a seed virus that is a precursor in a future vaccine against swine flu, the World Health Organisation said on Tuesday.

“There are currently four of our reference laboratories who are working with seed virus, they are at various stages of producing seed virus needed to make the vaccines,” said WHO spokesperson Gregory Hartl.

Hartl said however that the laboratories – in Britain, Canada and the United States – have not been asked to begin production in an extensive manner.
…
WHO on Monday recommended that the UN agency “take steps to facilitate the development” of a vaccine against the swine flu virus found in the latest outbreak that has likely caused more than 150 deaths in Mexico and has spread worldwide.

But the panel stopped short of recommending a complete shift in global vaccine production capacity, warning that it would be “prudent” to continue regular seasonal vaccine production as well.

A spokesperson in Paris for Sanofi Pasteur, a subsidiary of the French pharmaceutical maker Sanofi-Aventis, had said that the time needed to make a flu vaccine is about four months.

Scaling up production of a vaccine is another hurdle. The main approach is to grow the virus samples in time-honoured fashion in embryo chicken eggs, which is slow and clumsy.

Production capacity of flu vaccines has tripled since 2007 in response to the Sars and H5N1 scares, according to a WHO-funded study published in February.

– AFP

More from News24:

Egypt works on H5N1 chicken vaccine

In news that partially redeems the very controversial decision to cull the country’s pigs – apparently based on a need to regularise the industry, rather than panic over transmission from pigs – AFP details how Egypt plans to produce its own vaccine within two years.

A useful graphic explaining how reassortant viruses occur.

Information on how the virus may have originated:

New virus may be a hybrid

Last updated: Monday, May 04, 2009

The new virus that has killed as many as 177 people and spread globally is a hybrid that appears to have mixed with another hybrid virus containing swine, bird and human bits, US researchers reported.

Raul Rabadan and colleagues at Columbia University in New York analysed the published genetic sequences from the H1N1 virus that has brought the world to the brink of a pandemic. “The closest relatives to the virus we have found are swine viruses,” Rabadan said.

“Six segments of the virus are related to swine viruses from North America, and the other two from swine viruses isolated in Europe/Asia,” they wrote in the online journal Eurosurveillance.

The US Centres for Disease Control and Prevention said last week after discovering this virus in two US children that it had four virus types – two swine, an avian and a human component. It may be even more complex than that.

‘This strain looks like another hybrid’
Influenza viruses mutate constantly, and they also swap genetic material with one another promiscuously – especially if an animal or person is infected with two strains at once.

Rabadan’s team said this particular strain looked partly like another hybrid, or what scientists call a reassortant, virus. “The North American ancestors are related to the multiple reassortants, H1N2 and H3N2 swine viruses isolated in North America since 1998,” they wrote.

“In particular, the swine H3N2 isolates from 1998 were a triple reassortment of human, swine and avian origin.”

For those in search of graphics for their webinar/presentation on flu pandemics: from the US National Archives.

http://www.archives.gov/exhibits/influenza-epidemic/records-list.html

The Influenza Epidemic of 1918 via kwout

http://www.archives.gov/exhibits/influenza-epidemic/records-list.html

And for light relief away from deadly viruses:

“Who would win in a fight: Gandalf or Darth Vader? What about Neo versus Harry Potter?”

Posted in General, Influenza viruses, Vaccines: General, Viruses | Leave a Comment »

Is This The Big One?

28 April, 2009

28th April 2009:

It just HAD to happen.

There was the world’s attention, focussed on H5N1 bird flu from Asia as The Next Big One – including doom and gloom pronouncements from right here (and here) – and of course, another flu comes from another source, in another location entirely.  You can, however, as previously highlighted here in ViroBlogy, use Google “Flu Trends” to track it – and now Google Maps too (thanks, Vernon!).

Flu life cycle

Flu life cycle

So what do we know?  On the 27th of  April, the Mexican government admitted to some 150 deaths, and over 1600 people apparently infected, in an epidemic caused by an Influenza A H1N1 virus that appeared to be a reassortant of viruses from pigs, birds and humans.  The virus has been dubbed “swine flu”; however, there is doubt as to whether it has been shown to even infect pigs, let alone been found in them, and it probably ought to be known as “Mexico Flu”.  There is the problem, of course, that apparently parts of the virus – and the N1 gene in particular – are of Eurasian swine flu origin, so exactly where it comes from may be forever obscure.

 As for current expert knowledge, the Centers for Disease Control and Prevention (CDC) and the World Health Organisation (WHO) have set up dedicated pages to track the potential pandemic – because that is what they are calling it.

The WHO has, as of the 27th April,

“…raised the level of influenza pandemic alert from the current phase 3 to phase 4.

http://blogs.wsj.com/health/2009/04/27/understanding-the-whos-global-pandemic-alert-levels/

Swine Flu: Understanding the WHO’s Global Pandemic-Alert Levels – Health Blog – WSJ via kwout

The change to a higher phase of pandemic alert indicates that the likelihood of a pandemic has increased, but not that a pandemic is inevitable.

As further information becomes available, WHO may decide to either revert to phase 3 or raise the level of alert to another phase.

This decision was based primarily on epidemiological data demonstrating human-to-human transmission and the ability of the virus to cause community-level outbreaks.

Given the widespread presence of the virus, the Director-General considered that containment of the outbreak is not feasible. The current focus should be on mitigation measures.”

All of which begs the questions: what IS it, and how BAD is it??  We know that by the 28th April, the virus had been confirmed in the USA (>40 cases), Spain, Canada, and according the the BBC, the UK, Brazil and New Zealand as well.

While financial markets are panicking , airlines are cancelling flights, and people in Mexico appear to be dying, people infected in the USA seem only to be getting ill, and then recovering.

The bad news is that the virus haemagglutinin – the H1 – is probably only distantly related to that of the currently circulating human variant, so the flu vaccines on release right now will be of only limited efficacy.

The good news – especially for Roche and GlaxoSmithKline – is that the antivirals Tamiflu and Relenza seem to work against the virus.

29th April 2009

The virus continues to spread: according to the WHO site,

“As of 19:15 GMT, 28 April 2009, seven countries have officially reported cases of swine influenza A/H1N1 infection. The United States Government has reported 64 laboratory confirmed human cases, with no deaths. Mexico has reported 26 confirmed human cases of infection including seven deaths. The following countries have reported laboratory confirmed cases with no deaths – Canada (6), New Zealand (3), the United Kingdom (2), Israel (2) and Spain (2).
….
WHO advises no restriction of regular travel or closure of borders. It is considered prudent for people who are ill to delay international travel and for people developing symptoms following international travel to seek medical attention, in line with guidance from national authorities.“

There is also no risk of infection from this virus from consumption of well-cooked pork and pork products. Individuals are advised to wash hands thoroughly with soap and water on a regular basis and should seek medical attention if they develop any symptoms of influenza-like illness.

Of course, there is also the inevitable hype – and some humour (thanks, Suhail!):

With a byline reminiscent of the “Ebola Preston” which was coined to satirise the hype generated around the 1995 Ebola hype, we have

 30th April 2009:

…so of course, I talk to a journalist; and of course, I shouldn’t have…!  For an otherwise good article about pandemic preparedness in Africa [ignore the bit about no drug stockpile in South Africa, because apparently we have some], see here.  South Africans: look at info on influenza at the National Institute for Communicable Diseases (NICD) in Johannesburg.

The WHO yesterday raised the level of influenza pandemic alert from the current phase 4 to phase 5.  We owe the WHO Director-General, Dr Margaret Chan, for these comments:

“On the positive side, the world is better prepared for an influenza pandemic than at any time in history.

Preparedness measures undertaken because of the threat from H5N1 avian influenza were an investment, and we are now benefitting from this investment.

For the first time in history, we can track the evolution of a pandemic in real-time.”

From the BBC today:

In Mexico, the epicentre of the outbreak, the number of confirmed cases rose to 97 – up from 26 on Wednesday….

  • The Netherlands confirms its first case of swine flu, in a three-year-old boy recently returned from Mexico. Cases have also been confirmed in Switzerland, Costa Rica and Peru
  • The number of confirmed cases in the US rose to 109 in 11 states
  • Japan reported its first suspected case of swine flu
  • China’s health minister says that the country’s scientists have developed a “sensitive and fast” test for spotting swine flu in conjunction with US scientists and the WHO. The country has recorded no incidence of the flu yet.
  • The WHO says it will now call the virus influenza A (H1N1).

And first prize for over-reaction of the year:

On Wednesday, Egypt began a mass slaughter of its pigs – even though the WHO says the virus was now being transmitted from human to human [and there is no evidence it was ever transmitted between pigs].

 

 

Index: ViroBlogy / MicrobiologyBytes flu-related posts

Posted in Evolution, General Virology, Influenza viruses, Vaccines: General, Viruses | 1 Comment »

When is a virus not a virus?

3 March, 2009

A fascinating new post from Science Daily – for which, thanks Vaibhav Bhardwaj – raises again the problem of just exactly what is (and what is not) a virus?

The article in question describes a fascinating three-way interaction between a virus, a parasitic wasp, and a caterpillar – with a virus which happens to be part of the germline of the wasp, gets injected into the caterpillar as a free genome, and modifies its immune system so as to tolerate the wasp’s eggs.

From the article:

“Researchers have known for about 40 years that some species of parasitoid wasps inject these viruses, known as polydnaviruses, into the body cavities of caterpillars at the same time that they lay their eggs in the caterpillars. Because these “virus-like particles” have become an integral part of the wasp genome, some researchers have suggested they should no longer be considered viruses.”

Funny thing: that hasn’t stopped the International Committee on Taxonomy of Viruses (ICTV) from recognising as viruses agents such as Petunia vein clearing virus, a pararetrovirus (=DNA retrovirus) with an activatable integrated form, Banana streak virus, which is present in and activatable from the genomes of most Musa species, or even two whole  families of retrovirus-like retrotransposable elements in the Pseudoviridae and the Metaviridae.

So there is ample precedent for things that integrate into host genomes, that are also viruses – including, among vertebrates, where activatable endogenous retroviruses are the subject of much study – including a finding that prions may activate endogenous retroviruses in the human brain.

And what of polydnaviruses (family Polydnaviridae)?  Well, fascinating and unique beasts, these: the two genera so far described – Bracovirus and Ichnovirus – contain viruses which have a variable number of circular double-stranded DNA components, with components ranging in size from 2 to >31 kbp, for a total genome size between 150 – 250 kbp.  Both sets of viruses occur as integrated proviruses in the genomes of endoparasitic hymenopteran wasps, replicate by amplification of the host DNA, followed by excision of episomal genomes by site-specific recombination, and only produce particles by budding from (ichnoviruses) or lysis of (bracoviruses) calyx cells in the oviducts of female wasps during pupal-adult transition.  Moreover, the viruses in the two groups may well not be evolutionarily linked to one another, given that there is no antigenic or genome similarity, and the particles formed by the two groups are very different: ichnoviruses make ellipsoidal particles with double membranes containing one nucleocapsid; bracoviruses make single-enveloped particles containing one or more cylindrical nucleocapsids.  The latter may derive from nudiviruses, which appear to have contributed very substantially to wasp survival.

From another Science Daily article:

“What this means… is that nudiviruses infected wasps a few million years ago and that, over time, the viral DNA fully integrated into the wasp genome. As it currently stands, the wasps need the virus to survive, because the virus helps the insects lay eggs in caterpillars. The virus also needs the wasp to survive, because the virus can only replicate in the wasp’s ovaries. The virus cannot replicate inside the caterpillar, because all of its replication machinery is inside the wasp.”

 Particles are injected along with eggs into larvae of lepidopteran hosts; the DNA gets into secondary host cells and is expressed, but does not replicate -and this expression leads to some quite profound phsiological changes, many of which are responsible for successful parasitism.  The association between wasp and virus has been termed an “obligate mutualistic symbiosis”, and appears to have evolved over more than 70 million years.  It does nothing for the lepidopterans, however….

But nothing in this association would lead me to doubt their nature as viruses.  Viruses now dependent on a particular host, maybe, but there now appears to be a continuum in the virus life experience, from massive bigger-than-cell-genome mimiviruses, through parasitic viruses to tiny circoviruses – and including agents that have become irretrievably integrated into the genomes of other hosts, yet still have a partially independent existence, like pseudoviruses – and polydnaviruses.

Viruses are wonderful…B-)

Posted in Evolution, General Virology | 1 Comment »

Umm…no, they don’t

28 November, 2008

For shame, New Scientist!!  There I go recommending you to all and sundry – and especially my students – as a fount of general scientific knowledge, and you do this!!  In the 22nd November issue – freshly on my desk, down here in the Deepest South – there is, under the column heading “60 Seconds”, the following snippet:

Shot thwarts warts

A human papilloma virus vaccine already approved in women to prevent cervical cancer has proved equally effective in men against genital warts – which can lead to cervical cancer in women. In a trial of the vaccine in 4000 men only three recipients developed HPV-related lesions compared with 31 who received a placebo.

Note the bolded section: BECAUSE IT IS VERY WRONG. 

No, New Scientist, genital warts in men do NOT lead to cervical cancer in women: warts in men and women are caused by a number of what are termed “low risk” viruses (for low cancer risk), and especially by HPV types 6 and 11 – which are two of the types included in Merck’s Gardasil.  The other two types in this vaccine – which are the same ones as in GlaxoSmithKline’s Cervarix – are the high cancer risk HPV types 16 and 18.  Which do NOT cause genital warts, in men or women: rather, they cause inapparent infections of the epithelial tissue of the penis in men, and of the vaginal and cervical mucosa in women. 

The lesions can most often only be seen in both men and women after they have been painted with an acetic acid solution – hence the name “aceto-white lesion”.

The fact that warts are apparently prevented in men is a very welcome development: this means that in all likelihood the other infections will be prevented too, and men will not be able to transmit HPV 16 and 18 to women.

Which is presumably what you meant.

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Posted in Vaccines: General, Viruses | 3 Comments »

Despair

25 November, 2008

I have had much occasion to frequent the archives of Despair.com in search of demotivational posters with which to inspire my friends and colleagues…and now Alan Cann has given me the opening to display one of my better efforts.  He posted on a new Ebola virus found recently in western Uganda.

I will give you this….

ebola-poster1

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Do corals get stress headaches?

20 November, 2008

The large DNA viruses – pox-, irido-, herpes-, asfar-, mimi- and baculoviruses and their ilk – have a deep and possibly complex evolutionary history, and there is considerable evidence to suggest long histories of co-speciation with host lineages.  Indeed, the herpesviruses – including those of particular interest to humans , 1 and 2 and varicella-zoster (chickenpox) and 8 (associated with Kaposi’s sarcoma) – seem to have co-speciated along with vertebrates, with human and simian cytomegaloviruses, for example.

Now there comes evidence from a metagenomic study (which should, of course, be metaviromic) that invertebrates such as corals also have a a variety of herpesviruses, and that these may well be stress-activated: Rebecca Thurber and colleagues, in the 25th November issue of PNAS, have published an analysis of the incidence and effects of hitherto-unknown herpesvirus-like agents found in finger corals in Hawaii.  Their abstract:

Metagenomic analysis indicates that stressors induce production of herpes-like viruses in the coral Porites compressa

During the last several decades corals have been in decline and at least one-third of all coral species are now threatened with extinction. Coral disease has been a major contributor to this threat, but little is known about the responsible pathogens. To date most research has focused on bacterial and fungal diseases; however, viruses may also be important for coral health. Using a combination of empirical viral metagenomics and real-time PCR, we show that Porites compressa corals contain a suite of eukaryotic viruses, many related to the Herpesviridae. This coral-associated viral consortium was found to shift in response to abiotic stressors. In particular, when exposed to reduced pH, elevated nutrients, and thermal stress, the abundance of herpes-like viral sequences rapidly increased in 2 separate experiments. Herpes-like viral sequences were rarely detected in apparently healthy corals, but were abundant in a majority of stressed samples. In addition, surveys of the Nematostella and Hydra genomic projects demonstrate that even distantly related Cnidarians contain numerous herpes-like viral genes, likely as a result of latent or endogenous viral infection. These data support the hypotheses that corals experience viral infections, which are exacerbated by stress, and that herpes-like viruses are common in Cnidarians.

Yet another demonstration – after the viromes of whole oceans – of the sheer brute power of modern sequencing technology and bioinformatics techniques, applied this time to a disease problem of oceanic invertebrates.  The authors again:

Environmental stress often results in coral bleaching, disease, and death. Increased temperature, nutrient loading, dissolved organic carbon pollution, and reductions in ambient seawater pH are of particular concern due to their effects on the coral-symbiont relationship, host homeostasis, microbial overgrowth, and skeletal deposition. To determine whether environmental perturbations shift the eukaryotic viral assemblage present in corals, these 4 parameters were manipulated, and the resulting viral consortia characterized through the generation of 6 metagenomes [!]

Basically, they purified virus-sized particles from seawater, extracted DNA, verified there was no cellular DNA present (by PCR for 16S and 18S rDNA), and amplified the viral DNA using a GenomiPhi phi29 plymerase-based genome amplification kit from GE Healthcare, and sent to 454 Life Sciences for pyrosequencing.

What came back was obviously a mountain of sequence data – which was archived at the San Diego State Center for Universal Microbial Sequencing – and then analysed for contigs or assemblable runs of sequences which looked like herpesvirus or other genomes.  The supplemental data to this paper gives a relationship dendrogram – which isn’t that informative, as it contains just one coral thymidylate kinase sequence, and that is grouped within a clade with human viruses with other vertebrate herpesviruses outside of those.

The final story, then, is that the intrepid coral viromicers (horrible, I know, but come up with a better one?) succeeded in showing that stresses do indeed activate herpes-like viruses in coral.  In their words:

The metagenomic and temporal experiments presented here demonstrate that exposure to stressors results in the production of a herpes-like virus or a consortium of herpes-like viruses in P. compressa corals.  Thermal stress, eutrophication, and decreasing seawater pH have each been shown to disrupt coral health. Increases in sea surface temperature causes coral bleaching and increased coral disease incidence (58, 59). Nutrient addition exacerbates coral diseases, and reduced pH results in loss of corallite deposition (60, 61). This study demonstrates that, in addition to symbiont loss and bacterial and fungal disease (62), temperature and nutrient elevation and pH reduction result in increased HLV production.

Another, more fundamental speculative comment:

Herpesviruses typically infect nervous tissue, and it is tempting to suggest that the herpes-like viruses in Cnidarians may have ancient origins, because Cnidarians are the first metazoans to develop rudimentary nervous systems….

So be kind to our poor fronded friends…they may be our close cousins in discomfort when stressed.

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Posted in Evolution, General Virology | 2 Comments »

Zambia fever virus: latest

8 October, 2008

Latest links:

“120 people under observation for killer virus” SABC, October 8th

“Killer-fever link found by luck ” Independent On-Line 08-10-08

And just as a reminder that life goes on: a Congo fever patient from here in South Africa.

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Posted in General Virology, Uncategorized, Viruses | Leave a Comment »

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