ViroBlogy

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

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

The report goes on to say:

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

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

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

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

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

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

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

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

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

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

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

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

I blame Chris Upton

And that’ll go down REALLY well: European governments and policymakers pushing GM crops in Africa, when their own people don’t want them?  

Whether those reasons are stupid or not, and whether or not it is a good idea to plant GM in Africa, I can see a knee-jerk anti-Europe response could well work to completely screw up just what it is they are trying to do.

Consider: Zimbabwe and Zambia resolutely oppose even the import of GM maize as FOOD, let alone allowing the planting of it.  Africans have a history of being VERY suspicious of outsiders bearing gifts – because there is a history of dumping stuff in Africa, of everything from suspect pharmaceuticals to excess chickens.

I predict a lead balloon result for this conference and for the initiative.  Time for Europe to listen to the Kenyans, Burkinabe and South Africans about the merits of growing GM – and not the other way around!

This is actually horrifying, in the context of what is SUPPOSED to be Africa’s most developed economy – and especially its most developed agricultural economy.

Really: it is a fact not much appreciated outside of the agricultural sector, that we have to get our FMDV vaccines from BOTSWANA.

That’s right – the country with the largest economy in Africa gets its FMDV vaccines from the Botswana Veterinary Institute, a factory set up by the French in a country with a total population about a quarter of that of Greater Johannesburg.

So, let us get this straight: the country that owns the Onderstepoort Veterinary Institute, where the legendary Sir Arnold Theiler pioneered virus and other vaccines from the 1890s on, cannot make its own FMDV vaccines any more?

The country that USED to make a whole range of animal vaccines via the state-owned facility that is now Onderstepoort Biological Products, is now struggling to make just a few?

The country that once built a state-of-the-art BSL4 facility dedicated to FMDV now cannot operate it, or even make old-style killed vaccines?

Don’t let me get started on human vaccines, because we now don’t make ANY – but the erosion of our capacity to make vaccines means our ability to look after human and animal health is now severely under threat.

This is a good report about a VERY interesting finding – with one flaw.  They go on, apparently, about how BSMV is a "new virus": why would anyone think that?  Since the late 1980s, Adrian Gibbs and others have pointed out that tobamoviruses are probably ancient; just because RNA CAN evolve fast doesn’t mean it does, in terms of encoding functional elements.  Gibbs showed this for plant viruses; it has also been done for the HIV/SIV complex, where it is shown that a similar divergence in sequence among theses viruses to all animals since the Cretaceous, has led to NO changes in morphology, or gene function.

The simple fact is that having "plastic" genome in comparison to eukaryotic cells does NOT mean that ssRNA viruses may not be ancient.

Having said all that, it really is a tour de force to have sequenced a virus that old – aided by the fact, I am sure, that BSMV is hardy little beast, with a really stable vision.

Now, to find those hundred-year-old maize leaves put away with maize streak virus symptoms….B-)

Thanks to @Elsevier Microbiol* for pointing this out!

Yes.  Um.  Well.  I have just heard a lecture by the redoubtable Marc van Regenmortel (disclosure: my former mentor) pointing out how this strategy is highly UNLIKELY to be "the" way of generating antigens that are likely to be good immunogens – and I was convinced.

Now this.

Um, he said.  And…the MHvR arguments still stand, I think: why should something that supposedly looks like the thing that supposedly elicited a strongly neutralising antibody, elicit a strongly neutralising antibody?

OK, it apparently did here – but as a general rule?  Do we KNOW what "good" neutralising epitopes look like in 3D?  Because linear epitopes are really just an approximation to what real epitopes are, and epitopes are in fact just those things that BIND antibodies – NOT necessarily what ELICITS them.

Damn, I’m sounding like Marc – must be catching!

But seriously: antibodies are the membrane receptors of B cells; they are generated by random recombinations, and then selected by adventitiously binding another molecule that is not self; they are then further selected by repeated rounds of binding, while undergoing random mutations affecting their hypervariable regions, while weak binders are selected AGAINST by Tregs.

And end up both with higher affinity, and more broad binding to related "epitopes" as a result.

Incredibly hard to duplicate as general phenomenon, I would surmise.

Great infographic – and potentially good news.  But as I have told my students repeatedly since the mid-1980s, this is a long. slow pandemic – and we are only just over halfway through it.

There’s still a long way to go.

So THIS is the next one?  Possibly?  Good job they’re <a href="http://who.int/influenza/vaccines/virus/candidates_reagents/a_h7n9/en/index.html">already making vaccines</a>, then, isn’t it?