Archive for August, 2008

Big viruses have little viruses….

28 August, 2008

Just when you’d heard of mimiviruses, and thought it couldn’t get any stranger…the same team now bring you “mamavirus“, so named because it’s bigger!

But wait, that’s not all: apparently the new viruses have their very own “virophages” – smaller viruses which parasitise mamavirus-infected cells, and so called because they look like and have homology to bacteriophages.

And that’s still not all…Helen Pearson in the 6th August online Nature News then makes a case for viruses being considered as being alive, on the strength of this parasitism – and its detrimental effect on the larger virus, in terms of aberrant assembly, lower yield in infected cells, and so on.

Well, now…some of us have never thought otherwise, have we?  And despite all of the hype about how huge these viruses are, and how they blur the boundary between alive and dead – they don’t do they?  For all their complexity, mimi- and presumbably mamaviruses do exactly what all other viruses do: they obligately parasitise cellular organisms, and use their machinery (and especially ribosomes) to make viral components which asemble into particles.

And the news piece goes on:

“The discovery of a giant virus that falls ill through infection by another virus is fuelling the debate about whether viruses are alive.

“There’s no doubt this is a living organism,” says Jean-Michel Claverie, a virologist at the the CNRS UPR laboratories in Marseilles, part of France’s basic-research agency. “The fact that it can get sick makes it more alive.””

Ye-e-e-ssss?  Really?  And calling what is obviously a satellite virus – for all that it is a big satellite virus – a “virophage” is simply creating new terms where none are necessary.  Actually, they go one worse than that: the original article refers to the satellite as “Sputnik” throughout, in a breathtaking display of artistic licence.

But putting the outraged taxonomist in me aside, this is a truly amazing discovery, worth all of the hype: it shows that we really don’t know a lot about what is sitting in plain sight – in cooling tower water, in this case – let alone what is is sitting in deep oceans, in terms of viral biodiversity.

While the mamavirus is interesting enough, what should be called Mamavirus associated satellite virus rather than Sputnik, is even more so: satellite viruses are generally small and have very few genes, whereas this has 21 genes in a ~18 kb circular dsDNA genome, makes isometric particles 50 nm in size (which can be found within mamavirus particles), and in the words of La Scola et al.:

“…contains genes that are linked to viruses infecting each of the three domains of life Eukarya, Archaea and Bacteria. Of the 21 predicted protein-coding genes, eight encode proteins with detectable homologues, including three proteins apparently derived from APMV [Acanthamoeba polyphaga mimivirus], a homologue of an archaeal virus integrase, a predicted primase–helicase, a packaging ATPase with homologues in bacteriophages and eukaryotic viruses, a distant homologue of bacterial insertion sequence transposase DNA-binding subunit, and a Zn-ribbon protein. The closest homologues of the last four of these proteins were detected in the Global Ocean Survey environmental data set, suggesting that Sputnik represents a currently unknown family of viruses.  Considering its functional analogy with bacteriophages, we classify this virus as a virophage. The virophage could be a vehicle mediating lateral gene transfer between giant viruses.”

Fascinating indeed: this parasite upon a parasite – it replicates only in the “giant virus factory found in amoebae co-infected with APMV” – is bigger than many autonomous viruses infecting mammals, looks like it is at least partly derived from a bacterial virus in that it may integrate into its host (the mimivirus?) within a eukaryote, and may shuffle DNA around between other viruses.

I’m definitely working in the wrong field.

There’s gold in them old veins….

26 August, 2008

I have often spoken of “molecular archeology” in my lectures, and of the possibility of identifying past epidemic / pandemic strains of human flu in particular, by looking at which viruses are recognised by antibodies from people who lived through the epidemics.

A new paper in Nature ups the stakes in this game considerably: a team led by one James E Crowe Jr describes how 32 survivors of the 1918 Spanish Flu pandemic – born in or before 1915 – were “mined” for antibodies, and seven donors additionally were shown to have circulating B cells which secreted antibodies which bound the 1918 H1N1 virus haemagglutinin (HA).  The team isolated 5 monoclonal antibodies from these subjects, and showed that these potently neutralised the infectivity of the virus and bound the HA of a 1930 swine virus, but did not cross-react with the HAs of more recent human  H1-containing viruses.

Neutralizing antibodies derived from the B cells of 1918 influenza pandemic survivors : Abstract : Nature via kwout

 This achievement is undoubtedly a tour de force of modern molecular immunology – but is it useful?

Well, one very obvious fact is that people can obviously maintain significant levels of humoral immunity to viruses that infected them – in the words of the authors – “…well into the tenth decade of life.”  This is good news indeed for vaccinees who received vaccines for viruses which do not change much, like measles, mumps and poliomyelitis viruses.  However, given that influenza virus even of one H and N type can change so as to be unrecognisable in just a few years – the MAbs they generated did not react to any great extent with presumptively H1N1 human isolates from 1943, 1947, 1977 and 1999 – this is only of any use if the original virus were to be re-introduced somehow.

There was an intriguing statement in the paper which may shed some light on a long-running controversy as to the origin of the 1977 H1N1 pandemic, when the virus reappeared in humans for the first time since the early 1950s – allegedly as a result of an escape from a Soviet biowarfare lab.

The 1F1 antibody bound and neutralized the 1977 virus, albeit to a lesser degree than either the 1918 or the Sw/30 viruses … and to a minimal degree the 1943 virus”.

Ye-e-e-sssss…strange, that.  So the 1977 virus was antigenically more similar to 1930s era viruses than to one from 1943??

The proposed use of the findings also elicit biowar scenarios: for example, the fact that passive immunisation of people with antibodies to a particular virus can help them get over infection with it is purely academic for MAb to the 1918 virus – or is it?

I hope it is.