# What is Viral Fitness and How is it Measured?
**URL:** https://discourse.peacefulscience.org/t/what-is-viral-fitness-and-how-is-it-measured/12939
**Category:** Conversation
**Tags:** Science
**Created:** [January 3, 2021, 12:14pm UTC](https://discourse.peacefulscience.org/t/what-is-viral-fitness-and-how-is-it-measured/12939 "2021-01-03T12:14:10Z")
**Posts on this page:** 20
**Page:** 2
### Author:  [@Giltil](https://discourse.peacefulscience.org/u/Giltil)
#### Post date: [January 5, 2021, 7:42am UTC](https://discourse.peacefulscience.org/t/what-is-viral-fitness-and-how-is-it-measured/12939/22 "2021-01-05T07:42:06Z")
> [@Rumraket](#):
>
> So, it’s complicated, and there must be some relationship between different factors such as virulence, within-host reproductive rate, and transmissibility, where a virus has to trade off adaptations to successfully persist in some population in the long term
Agree. But in the case of flu, it would be difficult to argue for the adaptative value of evolution toward avirulence.
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### Author:  [@swamidass](https://discourse.peacefulscience.org/u/swamidass)
#### Post date: [January 5, 2021, 7:43am UTC](https://discourse.peacefulscience.org/t/what-is-viral-fitness-and-how-is-it-measured/12939/23 "2021-01-05T07:43:00Z")
We do see an adaptive pattern away from virulence in the case of the flu. That’s why vector species are so important in understanding the emergence of new virulent strains.
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### Author:  [@Giltil](https://discourse.peacefulscience.org/u/Giltil)
#### Post date: [January 5, 2021, 12:56pm UTC](https://discourse.peacefulscience.org/t/what-is-viral-fitness-and-how-is-it-measured/12939/24 "2021-01-05T12:56:03Z")
> [@swamidass](#):
>
> Of note, it seems Sanford/Carter measured fitness of flu using a measure of virulence…oops…
No, they don’t. I really invite you to read their paper to see that this is wrong. What they’ve done is to _examine the genetic changes arising within H1N1 from 1918 to the present_. And what they found is stated in their conclusion below:
_ **While there have been numerous adaptations within the H1N1 genome, most of the genetic changes we document here appear to be non-adaptive, and much of the change appears to be degenerative. We suggest H1N1 has been undergoing natural genetic attenuation, and that significant attenuation may even occur during a single pandemic. This process may play a role in natural pandemic cessation and has apparently contributed to the exponential decline in mortality rates over time, as seen in all major human influenza strains. These findings may be relevant to the development of strategies for managing influenza pandemics and strain evolution.** _
To sum up:
1. they document the numerous genetic changes that occurred in the H1N1 genome throughout its history.
2. they provide evidences that most ( but not all) of these genetic changes not only are non adaptive but also likely degenerative.
3. they note that the mutation accumulation is associated with the historical exponential decline in H1N1 human mortalities
4. by combining 2) with 3), they (rightly IMO) suggest that the decrease in the bug virulence, far from being adaptive, is due to genetic entropy.
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### Author:  [@Giltil](https://discourse.peacefulscience.org/u/Giltil)
#### Post date: [January 5, 2021, 12:56pm UTC](https://discourse.peacefulscience.org/t/what-is-viral-fitness-and-how-is-it-measured/12939/25 "2021-01-05T12:56:16Z")
> [@swamidass](#):
>
> We do see an adaptive pattern away from virulence in the case of the flu
What are the evidences for your claim?
The Sanford & Carter’s paper presents strong evidences of the contrary, I.e., that since its emergence in 1918, the H1N1 genome has linearly accumulated non adaptive mutations with time and that this phenomenon is positively correlated with reduced death rates.
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### Author:  [@Michael\_Okoko](https://discourse.peacefulscience.org/u/Michael_Okoko)
#### Post date: [January 5, 2021, 12:57pm UTC](https://discourse.peacefulscience.org/t/what-is-viral-fitness-and-how-is-it-measured/12939/26 "2021-01-05T12:57:14Z")
> [@swamidass](#):
>
> It’s a category error, because virulence/morbidity is not a measure of fitness
Even when positively correlated? How exactly are both apples and oranges in the context of viruses?
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### Author:  [@Giltil](https://discourse.peacefulscience.org/u/Giltil)
#### Post date: [January 5, 2021, 2:25pm UTC](https://discourse.peacefulscience.org/t/what-is-viral-fitness-and-how-is-it-measured/12939/27 "2021-01-05T14:25:30Z")
> [@dsterncardinale](#):
>
> There are also well-worn ways to measure relative fitness involving growing a reference strain and the strain in question for the same amount of time under the exact same conditions, and then allowing them to infect the same host cell population, and documenting their respective population sizes after some amount of time. Carter and Sanford also did not do this.
Carter and Sanford didn’t do this because it was impossible for them to do this.
> [@dsterncardinale](#):
>
> They made claims related to viral fitness
Not really. See my answer to @swamidass below:
[What is Viral Fitness and How is it Measured? - #24 by Giltil](https://discourse.peacefulscience.org/t/what-is-viral-fitness-and-how-is-it-measured/12939/24)
> [@dsterncardinale](#):
>
> So there is no basis for their claims
Basically, their claim is that most (but not all) of the mutations that has accumulated in the H1N1 genome throughout its history are non adaptive and even degenerative. And contrary to what you say, they provide evidences for this claim. So no, it’s not the FIN, not at all😉!
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### Author:  [@Rumraket](https://discourse.peacefulscience.org/u/Rumraket)
#### Post date: [January 5, 2021, 2:25pm UTC](https://discourse.peacefulscience.org/t/what-is-viral-fitness-and-how-is-it-measured/12939/28 "2021-01-05T14:25:46Z")
> [@Giltil](#):
>
> Agree. But in the case of flu, it would be difficult to argue for the adaptative value of evolution toward avirulence.
Why? It seems to me this facilitates the long-term persistence of the virus in the human population.
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### Author:  [@Giltil](https://discourse.peacefulscience.org/u/Giltil)
#### Post date: [January 5, 2021, 2:25pm UTC](https://discourse.peacefulscience.org/t/what-is-viral-fitness-and-how-is-it-measured/12939/29 "2021-01-05T14:25:58Z")
> [@Michael\_Okoko](#):
>
> Even when positively correlated? How exactly are both apples and oranges in the context of viruses?
I guess that human weight and height are positively correlated but they are not the same thing, right? The same apply to virulence and fitness. They often are correlated, but are not the same thing.
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### Author:  [@glipsnort](https://discourse.peacefulscience.org/u/glipsnort)
#### Post date: [January 5, 2021, 2:26pm UTC](https://discourse.peacefulscience.org/t/what-is-viral-fitness-and-how-is-it-measured/12939/30 "2021-01-05T14:26:33Z")
> [@Michael\_Okoko](#):
>
> Okay, so viral fitness is defined the same ways as for organisms, but I am guessing the specifics differ.
It’s defined the same way. The specifics that contribute to fitness differ, but the definition doesn’t. Absolute viral fitness (between hosts) is in fact just the basic reproduction number (R) that has become widely known during the pandemic.
> [@Michael\_Okoko](#):
>
> For example, a relatively more fit rat species will produce more offspring _using_ sexually reproduction. What is the virus equivalent?
Producing more offspring not using sexual reproduction. What’s the rat equivalent of producing more offspring using midwives, as humans do?
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### Author:  [@T\_aquaticus](https://discourse.peacefulscience.org/u/T_aquaticus)
#### Post date: [January 5, 2021, 3:39pm UTC](https://discourse.peacefulscience.org/t/what-is-viral-fitness-and-how-is-it-measured/12939/31 "2021-01-05T15:39:56Z")
> [@Michael\_Okoko](#):
>
> So virulence is just one factor influencing the fitness of viruses, but can it be used **alone** as a means of evaluating viral fitness?
Virulence is tangential to the question of fitness, in my estimation. It is a bit like asking if increasing the ability to fly is a factor in fitness. It might be true in birds and bats, but isn’t true in most lineages. What we are really asking is how a specific viral lineage competes against other viral lineages in the same population, and virulence may have nothing to do with it.
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### Author:  [@dsterncardinale](https://discourse.peacefulscience.org/u/dsterncardinale)
#### Post date: [January 5, 2021, 3:45pm UTC](https://discourse.peacefulscience.org/t/what-is-viral-fitness-and-how-is-it-measured/12939/32 "2021-01-05T15:45:44Z")
> [@Michael\_Okoko](#):
>
> What would be the reference and sample strains with regards to H1N1?
The 1918 strain (we have the full genome) against one of the more recent, lower-fitness (according to C and S) descendant strains.
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### Author:  [@Mercer](https://discourse.peacefulscience.org/u/Mercer)
#### Post date: [January 5, 2021, 3:46pm UTC](https://discourse.peacefulscience.org/t/what-is-viral-fitness-and-how-is-it-measured/12939/33 "2021-01-05T15:46:03Z")
> [@Giltil](#):
>
> What they’ve done is to _examine the genetic changes arising within H1N1 from 1918 to the present_.
What they’ve done is _ **misrepresent** _ the genetic changes. They are conflating reassortment with mutation.
> [@Sanford and Carter](#):
>
> These findings may be relevant to the development of strategies for managing influenza pandemics and strain evolution.
If they truly believed that, they would be developing such strategies, but they aren’t. Why?
> [@Giltil](#):
>
> The Sanford & Carter’s paper presents strong evidences of the contrary…
It misrepresents the evidence.
> [@Giltil](#):
>
> that since its emergence in 1918, the H1N1 genome has linearly accumulated non adaptive mutations with time
The graph isn’t linear and it conflates reassortment with mutation.
> [@Giltil](#):
>
> this phenomenon is positively correlated with reduced death rates.
That is objectively false. Fatality rates vary from year to year with no obvious trend.
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### Author:  [@Michael\_Okoko](https://discourse.peacefulscience.org/u/Michael_Okoko)
#### Post date: [January 5, 2021, 3:46pm UTC](https://discourse.peacefulscience.org/t/what-is-viral-fitness-and-how-is-it-measured/12939/34 "2021-01-05T15:46:18Z")
> [@glipsnort](#):
>
> The specifics that contribute to fitness differ,
This is what I asked for.
> [@glipsnort](#):
>
> Producing more offspring not using sexual reproduction. What’s the rat equivalent of producing more offspring using midwives, as humans do?
LOL, ignore this part. I had something else in mind, but typed it another way.
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### Author:  [@dsterncardinale](https://discourse.peacefulscience.org/u/dsterncardinale)
#### Post date: [January 5, 2021, 4:02pm UTC](https://discourse.peacefulscience.org/t/what-is-viral-fitness-and-how-is-it-measured/12939/35 "2021-01-05T16:02:31Z")
Okay, let’s do this in a wee bit more detail.
C and S claimed two things indicate a loss of fitness over time from 1918-2009: Lower virulence and decrease in host-specificity of codon bias.
I’ll start with codon bias, because, coincidentally enough, literally half my PhD thesis was on the evolution of codon bias in viruses. For RNA viruses, you know how strong translational selection is? (That’s selection to match the codon profile of your host, btw.) It’s basically non-existent. Which means that codon usage in RNA viruses is basically random, and substituting one codon for another is, as far as we can tell, completely neutral. There are some exceptions around the edges: Humans don’t like CpG dinucleotides, so we tend to see a loss in those codons over time; those changes are adaptive in the virus. And guess what? C and S documented many such changes. So much for being entirely neutral or harmful. So that’s codon bias. To the extant any of the changes would be non-neutral, it appears they would be beneficial.
And then virulence. Oh, virulence. C and S commit the very basic mistake of assuming greater virulence = more fit. Ask an epidemiologist if that is a reasonable assumption.
Virulence correlates with fitness based on the ecological context in which a virus exists. If there are a TON of susceptible hosts readily available, then the limiting resource is cells to infect within each host. This is called intra-host competition. To be successful (i.e. for your genotype to propagate), you need to win the competition within your current host. That means infecting fast and making a lot of offspring as fast as possible. This will likely be very harmful to your host, but that doesn’t matter, because there are plenty more where that came from.
But what happens after like half the population has been infected and is now either dead or immune? Turns out, hosts can be a bit harder to come by. That means the rate-limiting step in your life cycle isn’t being the best within your current host anymore. Now the problem is getting to a new host. So what happens if you’re _really_ good at competing in your current host, and therefore _really_ deadly? _Exactly_. You kill your current host before any offspring can spread to a new host, and now your genotype is extinct. In this situation, it’s _inter-host_ competition that matters; you’re competing with viruses _in other people_ for access to the few remaining susceptible hosts. Under these ecological conditions, a better strategy is often lower virulence, less sick, less dead host, more opportunities to transmit.
This is _exactly_ what happened with the 1918 pandemic. That strain did not vanish in 1919 or 1920. Nor did we suddenly get REALLY good at treating influenza and the secondary respiratory infections. But the mortality rate plummeted because the selective pressure on the virus flipped from intra-host competition to inter-host competition as the pool of susceptible hosts shrunk. And I will note for good measure that these changes are not just “breaking” stuff. Virulence is a phenotype that is very tightly regulated. The rate of viral replication and number of progeny are tightly regulated. (I once saw a really cool talk on this called “How A Virus Counts To 1000”.)
C and S consider precisely _none of this_. They just assume, for absolutely no good reason, that higher virulence = more fit.
So no, this is not an open question. They got basically everything wrong they could possibly have gotten wrong when characterizing the evolution of the 1918 pandemic influenza strain.
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### Author:  [@Michael\_Okoko](https://discourse.peacefulscience.org/u/Michael_Okoko)
#### Post date: [January 5, 2021, 4:38pm UTC](https://discourse.peacefulscience.org/t/what-is-viral-fitness-and-how-is-it-measured/12939/36 "2021-01-05T16:38:35Z")
Cool points. I am definitely going to convert this page to PDF when it is closed. Its an excellent resource.
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### Author:  [@Michael\_Okoko](https://discourse.peacefulscience.org/u/Michael_Okoko)
#### Post date: [January 5, 2021, 4:38pm UTC](https://discourse.peacefulscience.org/t/what-is-viral-fitness-and-how-is-it-measured/12939/37 "2021-01-05T16:38:39Z")
> [@dsterncardinale](#):
>
> The 1918 strain (we have the full genome) against one of the more recent, lower-fitness (according to C and S) descendant strains.
Good point. Thanks.
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### Author:  [@Michael\_Okoko](https://discourse.peacefulscience.org/u/Michael_Okoko)
#### Post date: [January 5, 2021, 4:38pm UTC](https://discourse.peacefulscience.org/t/what-is-viral-fitness-and-how-is-it-measured/12939/38 "2021-01-05T16:38:44Z")
> [@T\_aquaticus](#):
>
> What we are really asking is how a specific viral lineage competes against other viral lineages in the same population, and virulence may have nothing to do with it.
Key point. Thanks.
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### Author:  [@Giltil](https://discourse.peacefulscience.org/u/Giltil)
#### Post date: [January 5, 2021, 5:49pm UTC](https://discourse.peacefulscience.org/t/what-is-viral-fitness-and-how-is-it-measured/12939/39 "2021-01-05T17:49:15Z")
> [@dsterncardinale](#):
>
> C and S claimed two things indicate a loss of fitness over time from 1918-2009: Lower virulence and decrease in host-specificity of codon bias.
This is wrong, for they indicate 2 other evidences in addition to the 2 you mentioned, that is1) the extinction of all human influenza strains existing prior to the H1N1 strain; and 2) the apparent extinction of the human lineage of H1N1 in 1956, and then again apparently in 2009.
> [@dsterncardinale](#):
>
> For RNA viruses, you know how strong translational selection is? (That’s selection to match the codon profile of your host, btw.) It’s basically non-existent
This is surprising. Do you have publications that support this point?
> [@dsterncardinale](#):
>
> Which means that codon usage in RNA viruses is basically random, and substituting one codon for another is, as far as we can tell, completely neutral
Then, why was there a codon bias in H1N1 in the first place?
> [@dsterncardinale](#):
>
> Humans don’t like CpG dinucleotides, so we tend to see a loss in those codons over time; those changes are adaptive in the virus. And guess what? C and S documented many such changes
Where did C and S document these changes? As for me, it has escaped my attention !
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### Author:  [@swamidass](https://discourse.peacefulscience.org/u/swamidass)
#### Post date: [January 5, 2021, 5:50pm UTC](https://discourse.peacefulscience.org/t/what-is-viral-fitness-and-how-is-it-measured/12939/40 "2021-01-05T17:50:06Z")
> [@Giltil](#):
>
> that is1) the extinction of all human influenza strains existing prior to the H1N1 strain;
Huh? There are many influenza strains that did not go through extinct…
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### Author:  [@dsterncardinale](https://discourse.peacefulscience.org/u/dsterncardinale)
#### Post date: [January 5, 2021, 6:11pm UTC](https://discourse.peacefulscience.org/t/what-is-viral-fitness-and-how-is-it-measured/12939/41 "2021-01-05T18:11:59Z")
> [@Giltil](#):
>
> This is wrong, for they indicate 2 other evidences in addition to the 2 you mentioned, that is1) the extinction of all human influenza strains existing prior to the H1N1 strain; and 2) the apparent extinction of the human lineage of H1N1 in 1956, and then again apparently in 2009.
First, the reason strains come and go is called strain replacement and it happens all the time, as a consequence of the dynamics I described in my longer post. If you’re well adapted for inter-host competition, what happens when a new strain to which very few people are immune appears? It outcompetes you within each host and becomes the dominant strain. But more importantly, there were and continue to be many strains that circulate at varying frequencies. Check the CDC advisories going back each year. C and S should have - they would have found their supposedly extinct strain in circulation.
> [@Giltil](#):
>
> > [@dsterncardinale](#):
> >
> > For RNA viruses, you know how strong translational selection is? (That’s selection to match the codon profile of your host, btw.) It’s basically non-existent
>
> This is surprising. Do you have publications that support this point?
Love when I get to cite [one of my own papers.](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3564115/)
> [@Giltil](#):
>
> Then, why was there a codon bias in H1N1 in the first place?
There’s always codon bias. The thing is what’s driving it? Biased mutation rates, translational selection, enzymatic activity, biased repair mechanisms, etc. For RNA viruses, “translational selection” is not the answer, as C and S seem to think it should be.
> [@Giltil](#):
>
> Where did C and S document these changes? As for me, it has escaped my attention !
Figure 7.
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