so influenza virus is a respiratory illness that affects people all around
the world around ten to fifteen percent of every single person in the whole
world population get infected with flu every year causing maybe half a million
deaths each year just from seasonal flu alone
and then of course every few decades we have one of these explosive pandemics
where the people that get affected by that tend to be young adults the virus
sweeps through the world very rapidly and for all those reasons we need to
have good control measures we need to understand the virus we need to know how
it replicates inside the body
why it causes disease and how it spreads from one infected host be it human or
animal to the next. Ferrets are used widely in flu research and they are
naturally susceptible to the same viruses as humans are and that's really
important because it means that they are a good animal model we don't have to adapt
the virus or change it in any way you can take the same virus out of a
person's nose
that's making them sick and inoculate it into a ferret and it will replicate in
the ferret's cells in the nose of the ferret
we also like to use ferrets for flu because they do actually show similar
clinical signs to the sorts of symptoms we see in people
so ferrets will get an upper respiratory tract infection
they'll get a mild fever and they'll feel lethargic at least we think they do
because they curl up in their cage
they will have a runny nose
and a cough, they will sneeze towards the end of the infection as well
the virus is a tiny fragile particle really that just contains its genome and in
order to infect a person the virus needs to gain access to the cells of the body
the upper respiratory tract
when it's replicated in that first person in order to survive really the
virus has to come out from that person and into the next and for flu that
is usually through droplets they breathed out into the air and they will survive a
small droplets in the air until somebody else breathes them in and takes them
into their respiratory tract and then the virus has access to the cells and
their respiratory tract so that's transmission process transmission
through the air
we understand is really key to the ability of ours to spread and cause
these outbreaks of seasonal flu and pandemics. We use ferrets to study that
because we can infect one ferret with a strain of human flu
we can place the second animal in a room sharing the same air but not necessarily
in the same cage and we can see that the ferrets themselves breathe out the virus
in their droplets of air and and can pass the virus from one animal to the
next
at the moment it's really difficult to recapitulate that experiment using cell
cultures you
you sort of really do need one animal to produce the virus and one animal to
receive it if you're going to study the entire process but we are working on
methods to break the process down and at least remove some of the animals
for example we recently been successful with funding from NC3Rs to replace the
sentinel animals
the ones that are going to receive the virus with cell culture dishes and we've got
a new piece of equipment that we've designed which we can place one infected
animal in and then the air from that animal is passed over the surface of
susceptible cell cultures and then we can read out whether those cell cultures
get infected by the virus and that is a semi in vitro semi cell culture method
for studying transmission. When we're going to infect ferrets with our known
sample of influenza virus we dilute the virus down so that we're only putting a
small number of infectious particles into the animal because that's really
what would happen to an animal or a person naturally acquiring the virus and
then we lightly anesthetise the ferret and just place a small droplet of
solution containing the virus into their nose they sort of breathe that in quite
naturally while they are likely under anesthetic and that virus in the liquid
has access to the cells of the upper respiratory tract which is the target
cells that the virus is going to infect and initiate the infection with if we
use a reasonably low dose of virus one that we think represents the type of
dose you would get exposed to - a natural exposure
the animals don't get very sick at all and we can see that they have after
three or four days a crusty nose sometimes a runny nose and sometimes
when we walk into the room
can hear them sneezing generally speaking with human influenza a sort of
typical seasonal strain much like an average person a ferret given a
normal dose won't get terribly sick
so we're very interested in how transmission happens there are two
aspects that we have recently been excited about one is the timing of
transmission so because we can monitor each day how much virus is present in
the nose and whether or not that virus is successfully being aerosolized and
making it across into the next animal we can see that transmission at least in
our ferrets happens very early in fact transmission from one animal to the next
happens most efficiently in the very early days one or two after we first
infected with the doner animal we have shown that the timing of transmission
absolutely correlates with the ability of the virus to come out into the air
and float in the air for enough time to survive and that's of course in ferrets
what we now want to do is to also move across into humans and ask whether that
that's also the case in humans because that would be very reassuring that the
ferret kinetics are telling us the same and we've got some exciting plans to be
able to do that - to actually infect human volunteers with doses of flu
and get them to breathe into the same piece of equipment and asked what day
after their infection are they most contagious
influenza virus is a difficult virus to control and work with and out there in
the community because it changes all the time it's always evolving and even if we
have a vaccine one year which protect people against viruses that are out
there
the following year the viruses will have evolved and changed we call that process
drift
so we're very interested in studying how that evolution happens and in order to
do that there are a number of parameters we need to know about one is
when the virus is transmitted from one host ferret or human to the next
first and how many virus particles actually do make it across and initiate
infection in the next host that has a big bearing on how fast something
can evolve
we call that sort of like a bottleneck if there are only one or two viruses
that initiate the infection there could be a very tight bottle neck and that
would have big implications
so we've been working on that using our ferret model we can infect one
animal with a mixture of viruses that we can count very easily and then we can
expose the next animal to that infected animal and we can ask does the whole
mixture come across and if it did that would mean that a lot of viruses must
move across statistically speaking or in the animal that catches influenza
from the one it's in the adjacent cage are they just only one or two types of the
viruses that we originally put into the first animal
incredibly it looks as if only a handful of virus particles are enough to
initiate infection in the next animal
humans are protected from flu if they need to be protected from flu by using
vaccines. All children aged two to three years old being taken out of their gps
for a live attenuated flu vaccine every year and also some of the primary school
children are receiving it in some pilot studies that are being run and actually
the point here is that the children are not really at a massive risk themselves if
they get flu they will get sick but not so bad but the point is that they are
going to be protected against the virus in the community and won't bring it home
to mom, dad or more importantly granny or grandpa who really are
at risk and in the pilot areas so far that looks incredibly effective all of
those vaccines rely on ferrets actually for their generation
it's very interesting but because we know that ferrets are susceptible to
human viruses they make antibodies after they've been infected with flu and the
serum that contains those antibodies is used by the world health organization
every year to try to predict whether or not we need update the flu vaccine for
the following year or not
so ferrets are absolutely key because they're susceptible to all the same viruses
as us and because they make antibodies in the same way that we do are absolutely key
to our ability to actually make vaccines and protect people