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How Attenuated Viruses Become Virulent / Cell, March 23, 2017 (Vol. 169, Issue 1)

the summary figure does a great job

describing the findings yes I also like

it it illustrates well the evolutionary

mechanisms of the epidemics do you mind

if I ask what you guys are working on

sounds pretty exciting we were just

chatting about our recently published

studies on poliovirus yes it could

definitely help with the polio

eradication campaign

I thought polio was eradicated years ago

don't we have a vaccine for that already

yes we do have a very effective vaccine

but the job is not completely done what

so vaccines don't work of course they do

but we haven't completely eradicated the

polio virus and until we do there's

always a risk that it will come back

with the same force of years ago when it

caused paralysis and more than 100,000

children a year the vaccine is given

orally and provides very robust and

long-lasting protection because it's

based on a live benign virus one that

does not cause disease but induces very

good immunity it replicates in the

recipients gut mimicking natural

infection and inducing mucosal immunity

at the site of replication thus it

blocks transmission from person to

person that's great to control the

spread of the virus and may even

eradicate polio virus from the face of

the earth the problem is that sometimes

the vaccines benign virus reverts to a

fully fit and virulent strain that can

once again circulate through human

populations there have been numerous

outbreaks over the years to finish the

job we need to understand how this

happens

I see the idea is to learn how the

vaccine strains evolved to a virulent

strain interesting yes and what is

interesting in our study is that there's

only one ancestor to all vaccine derived

virulent strains so we know where we

start vaccine strain and where we end up

circulating virulent strains that

provides a unique opportunity to study

if the virus gets more pathogenic using

similar evolutionary paths

isn't this your floor I'll get it on the

way back down this is really interesting

so what exactly did you find

well we developed a mathematical model

to identify mutations driving the loss

of attenuation and regain of virulence

in the vaccine strain and we found that

more than 30 outbreaks around the world

very similar evolutionary trajectories

were used the same mutations drive the

path to virulence even the temporal

order in which the mutations are

acquired by the virus and its way to

virulence is similar in all these

independent outbreaks the way that the

vaccine virus regained virulence is by

first acquiring what we call gatekeeper

mutations only three are needed then the

polio recombines with other Co

circulating benign viruses and then the

virus further improves fitness by

incorporation of a few additional

mutations here and there but to me the

most provocative finding is that we can

simulate the same evolutionary

trajectory in very simple cell culture

conditions the idea is that perhaps we

can understand virus evolution and

epidemics and similar experimental

models so you could predict the

evolution of viruses well that would be

great but we hope that at least this

helps us to understand the basic

principles that rule the virus evolution

and who knows perhaps one day we could

control it

seriously guys it's an elevator not a

classroom

you