Helps Prevent Mutations From Occurring Over and Over Again

How viruses mutate and what tin can be done about it

Virologist Andrew Pekosz discusses what nosotros know then far about coronavirus variants and what they mean for our understanding of SARS-CoV-2 overall

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Published

July xix, 2021

Fifty-fifty as some Americans resume pre-pandemic activities like social gatherings or dining or shopping mask-free, a perilous schism is emerging in the U.S. between those who are vaccinated against COVID-19 and those who are not. And circulating almost exclusively amidst those who are unvaccinated is a potential threat to everyone: coronavirus variants.

U.S. cases of COVID-19 accept more than than doubled in the past ii weeks, with the delta variant accounting for more than than one-half of new infections, according to the Centers for Disease Control and Prevention. Virus variants themselves are not unexpected—viruses mutate oftentimes, and occasionally a new course provides enough viral advantages that information technology can take hold and spread throughout a community. Simply the rapidity with which new viral strains of SARS-CoV-2 are emerging suggests that the greatest tool in the public wellness arsenal now is vaccination, which would prevent infections—and further viral mutations—from occurring in the first place.

"Say, for example, it's a one in a million chance that a mutation will be advantageous to the virus. If you allow the virus replicate itself 900,000 times, odds are that the advantageous mutation will occur," says Johns Hopkins virologist Andrew Pekosz. "But if yous limit the overall replication of the virus to 1,000 times, then it'southward much less probable that the random advantageous mutation is going to occur. And that's where public health interventions really assist us a lot during this pandemic—by reducing the full corporeality of virus replication and therefore reducing the chances that the virus can improve or adapt."

The Hub spoke with Pekosz for more insights into virus variants, how they emerge, and what can exist done to prevent them.

What makes the delta variant different from the other strains of coronavirus currently circulating in the U.S.?

Nosotros have some ideas, only we don't know everything nigh what's inverse with delta to make information technology more transmissible. We know that if we look at the spike protein, which is the protein the virus uses to attach to cells and start the infection process, we see that there are mutations that make that poly peptide ameliorate at entering human cells. We tin also look at the fasten poly peptide and see mutations that should reduce the ability of some of the antibodies generated by the vaccine to demark to the virus. So nosotros call back it's also finding ways to go around the immunity that we're generating in the population through vaccination.

Image caption: Andrew Pekosz

Prototype credit: Will Kirk / Johns Hopkins University

Merely the virus likewise has lots of other mutations in other genes, and nosotros don't know what those mutations might exist doing. So we accept some clue as to the changes that are happening, only labs like mine and many others across the land are spending a lot of time trying to figure out what else has changed in this virus to make it more than transmissible in the population.

A change to the spike protein, which is what vaccines target, is somewhat frightening.

Absolutely. But you know, when we look at the changes that are in the fasten, some of them are changes that nosotros've seen with other variants at other times. That gives u.s. the sense that there are a few mutations that requite the virus an reward—they make the virus better at transmitting or they help evade some immune responses that would normally forbid infection. And therefore those mutations start to appear in the populations that we're sequencing. And again, some of those mutations nosotros've seen in other variants at other times, and so it'due south telling usa that the virus is "learning" to optimize the pathway and it's finding the same types of mutations that mediate amend entry and meliorate replication.

But that also means that because the same "dangerous" mutations to the fasten protein occurred in other, less deadly variants, the spike mutation lone isn't what causes a variant to spread. Information technology takes a combination of factors.

Aye, absolutely. And that'south where looking at the virus genome itself only gives u.s.a. role of the motion-picture show. Ofttimes, other factors include where those mutations occur in the earth. Is information technology occurring at the right time? Is it occurring in a state of affairs where the virus tin become dominant? Are there other strains to compete with it at that fourth dimension? All those other factors play into whether a variant emerges and becomes dominant. And then information technology's really a complicated scene.

"To see something like [a new variant] emerge and out-compete other virus lineages is something that actually catches the attention of virologists every bit something to be concerned about, because it is such a difficult matter for a virus to take hold of upwardly to and surpass other lineages that take had a head start."

To see something like the D614G variant outset, then the blastoff variant and now the delta variant, emerge and out-compete other virus lineages is something that really catches the attention of virologists as something to be concerned virtually, because it is such a difficult thing for a virus to take hold of upwardly to and surpass other lineages that have had a head starting time.

How speedily exercise variants emerge?

Well, first, viruses take a mutation rate that'due south much, much higher than humans or other animals, and they replicate at a rate that'due south actually, really fast. So in other words, i virus-infected jail cell makes 100,000 copies of itself, and all those copies can go out and starting time replicating. And so mutations occur randomly, but considering the virus replicates at such a fast charge per unit, you likewise accumulate mutations actually fast.

Just again, it'southward important to annotation that while mutations occur randomly, almost of those mutations either do goose egg to alter how a virus behaves or they're detrimental.

Over the first year of the pandemic, we saw a lot of these mutations popping up that were allowing us to track the virus. We could say that a certain mutation occurred in England in this month and that virus strain started to spread. And we could trace back where viruses came from based on these unique mutations, but none of them really changed the manner the virus itself replicated. It's only now that we're getting into some of these variants that are irresolute the style the virus behaves in the population. And again, that'south just a really small ready of all the mutations that accumulate in these viruses.

Is it possible to prevent a virus from mutating?

Well, you can't forestall the virus from mutating, just what yous can do is limit the virus'southward spread, and in that way yous reduce the chances that a mutation tin can sally that is going to assistance the virus infect humans amend.

Say, for example, it's a one in a meg chance that a mutation will be advantageous to the virus. If you let the virus replicate itself 900,000 times, odds are that the advantageous mutation will occur. Simply if you limit the overall replication of the virus to ane,000 times, then it's much less likely that the random advantageous mutation is going to occur. And that's where public health interventions really assist us a lot during this pandemic—by reducing the full corporeality of virus replication and therefore reducing the chances that the virus can improve or accommodate.

So, if we can reach a critical mass of vaccination, we can presumably drastically reduce the chance that additional advantageous mutations will take hold in our communities.

"If you've gotten the total course of mRNA vaccine, y'all've got pretty good protection against these variants. And that'due south just one more piece of data to encourage people to go and become vaccinated."

Absolutely. And I remember we're seeing that now across the U.South., in places where there are good vaccination rates, you're seeing that the virus isn't spreading equally easily. Information technology's only spreading in unvaccinated people. And then the strength of vaccination in terms of not just protecting people, simply now limiting the emergence of other variants past reducing the overall replication of the virus in the population is clearly seen.

Equally new strains go identified—there'south now a gamma variant, likewise—what are we learning virtually the original SARS-CoV-2 virus?

Essentially it's telling us that that original strain—which surprised us with how well it was able to spread in the human being population—nevertheless has room for improvement. The basic Darwinian principles of natural pick are in play at present. The virus is changing to be able to spread better in the population, and when it gets better at spreading, information technology becomes the ascendant virus—and we're seeing that occur over and once again. So conspicuously this virus came in with a good ability to replicate in humans, only it'south finding ways to get meliorate and become more of a man pathogen as opposed to what we used to telephone call a zoonotic pathogen. This probably means it's going to exist a human pathogen for some time to come.

Practise you expect your lab to continue studying SARS-CoV-2 for a long fourth dimension?

Admittedly. My lab has spent a lot of time studying flu, and many of the same types of experiments that nosotros practice with SARS-CoV-2 give us very dissimilar results than the same experiment done with influenza. And then while those two viruses spread in the same mode and are causing illness in the respiratory tract, they exercise things in very different means. And then it'southward going to be very of import for us to understand how 2 respiratory viruses tin cause such different affliction at the molecular level.

While there's already been thousands of papers published on SARS-CoV-2, I call back we've merely scratched the surface in terms of understanding how this virus is causing harm in people—we don't really understand that in any detail. Comparing information technology to other respiratory viruses is going to be something that'south really, really important for us to do because, again, that's going to tell u.s. different signatures that we may demand to look for in animate being viruses that may tell us whether or non an animal virus is potentially a human pathogen.

But I would emphasize the important affair, which is the vaccines are all the same working, and the vaccines are working against the delta variant—particularly the mRNA vaccines. If yous've gotten the total course of mRNA vaccine, you've got pretty skilful protection against these variants. And that's simply one more piece of data to encourage people to become and get vaccinated. These vaccines for COVID-xix overall perform much better than I think any of the states scientists would have expected, and we actually accept a tool here that can brand a big departure right now—nationally, but soon globally—in how this virus is spreading.

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Source: https://hub.jhu.edu/2021/07/19/andrew-pekosz-delta-variants/

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