The Hepalogue

Quasispecies!

by The Golden Phaeton on 16/05/2016

If you are harbouring any doubts over the high-strangeness of the Hep C Virus, it’s time to consider quasispecies.

Once you’ve finished reading, you will have either a more profound appreciation of the breathtaking complexity of life – or further confirmation that the virus is the front end of an extraterrestrial invasion.

From the outset, it’s important to recognise a couple of things. Firstly, that what we call the Hepatitis C Virus (HCV) is as much a dark brotherhood of related viruses as something we would ordinarily consider a species in itself (i.e. a cat). Secondly that, although we know much about the disease, a great deal remains to be discovered.

quasispecies-image-for-web-final

One of the reasons for pre-treatment blood tests is to determine which of the six-plus genotypes one is hosting (some think there may be as many as eleven). Genetic variance among the genotypes is around a third. This is a lot. I’m not entirely certain if it’s a fair comparison, but consider for a moment that humans and chimps vary only by one per cent.

Genotypes 1 and 3 are the most prevalent in our country and are treated with different suites of medications. Within these genotypes, there are more than seventy branching subtypes. The presence of the better understood and most common of these (1a, 1b etc.) may also point to treatment strategies.

Beyond the subtypes, however, lie the quasispecies and here all that is familiar breaks down. Quasispecies are mutants and mutate is what HCV does – rapidly and by the trillions.

HCV is a master of the fast-and-loose reproductive strategy. As a single-strand RNA virus, there is no proof-reading when each virion copies itself (more than a trillion times a day). Mistakes proliferate and are themselves copied, always at the same astonishing rate.

Of course, this leads to a percentage of non-viable copies. But HCV still retains – after vital structural/reproductive areas are conserved – enormous room for variability, and the resultant hordes of variants (far too many to name beyond vague identifiers) are what we call quasispecies.

Generally, when a particular quasispecies becomes dominant in the host’s body, it is attacked and destroyed by the immune system. But then another quasispecies immediately oozes into the gap, and the body must remount its defences.

And so on down the track.

How many of these quasispecies in your body? Likely thousands, perhaps millions – depending on how long you’ve been infected and how much selective pressure your immune system has put on the virus. A percentage of these quasispecies are – like your immune system – unique to you.

This numerical strength contributes to Hep C being so successful as a chronic disease. It is very unlikely that your immune system will ever triumph against the never-ending ranks of enemy combatants arrayed before it – each one a novel challenge.

Indeed, given the frequency of immune-related disorders among those infected with Hep C, it seems that your immune system may sometimes misfire under the continuous pressure.

The theory of quasispecies began, strangely enough, as an attempt to describe the first appearance of large, complex molecules on Earth. Now, it has become an important model in the field of evolutionary virology.

When virus mutate – as many do – at a fantastic rate, the concept of ‘survival of the fittest’ becomes effectively meaningless. Selective pressure operates instead on ‘clouds of mutants’ in a way that would never be possible among what we normally think of as a ‘species’.

Amazingly, Hep C researchers – in their ongoing efforts to improve treatments – do seem to be moving beyond subtypes, and are identifying quasispecies, I gather, by their tendency to mutate/conserve at certain sections of the viral genome.

But, from this point on, the subject becomes so complex that I find it difficult to properly understand, let alone describe. Here’s a link, if you’re brave:

The quasispecies concept

And another, if you’re thinking of moving into virology – https://en.wikipedia.org/wiki/Viral_quasispecies

Let’s just thank science for the new treatments – the DAAs (Direct Acting Anti-virals) which specifically attack those areas of the HCV genome which are necessary for viable reproduction – neutering the virion and moving on, leaving a battle-weary immune-system to mop up the eunuchs.

Now it’s easy to throw words like ‘trillions’ about, but when you actually focus down on them, how can you not feel a sense of awe? The microscopic world is truly a wonder. Consider this: there are, it is thought, 1031 viruses on our planet. This is – to quote – a hundred million times more viruses on Earth than there are stars in the universe.

It’s amazing that any of us are still alive.

The Golden Phaeton

PS – I’ve simplified something insanely complicated here. Please, don’t be afraid to correct me, if you know better, in the comments below.

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