it’s a pleasure to be here with you
tonight for two reasons one is that
you’re such a lovely audience and I’m
I’ve got the pleasure of meeting most of
you in person and two is because
probably my parents are watching this
right now and they did wondering for so
long what on earth why we doing hungry
for all these years so it is time that
they actually know we’re talking today
about HIV the story started about a
century ago this is where a simian virus
a virus it was only infecting primates
such as monkeys were affecting the
chimpanzees somewhere in Africa now in
multiple types of the simian virus have
infected the chimpanzee monkey
recombination happened and this means
that there was an exchange between
genetic material between the viruses and
after this recombination a new virus was
born and that was able to cross infect
other species such as humans this was of
course the HIV one that causes the
devastating disease that we know as AIDS
or acquired immunodeficiency syndrome
around that time the recombination of
the simian virus is in another type of
monkey which is called the mangabey
monkey present in western Africa and
some parts of Central Africa as a result
in the evolvement of the HIV type two
there I’m quite sure that not many of
you know so Hance is going to be my
topic there’s a great difference between
the two viruses yes they have evolved
from the same ancestor which is a simian
virus however we know that there’s a
great genetic difference between the two
viruses there are about forty to sixty
percent difference in the genetic
sequence between the two viruses this
has resulted in genes being present in
one and not the other the difference in
the genetic sequence has led to
variability in the clinical spectrum
between the two viruses while HIV one is
regarded as the most aggressive type of
the two viruses it tends to cause AIDS
which is the disease much much faster
than HIV – if you’re infected by HIV one
you will develop AIDS within five to ten
years
whereas if you infected with HIV – it
tends to integrate into chromosomal DNA
for quite a longer period 10 15 20 years
even without treatment and most
importantly since the HIV – has evolved
from mangaboos monkeys in western Africa
we thought that the number of patients
infected is quite limited let’s say
about one to two million are going to
the roughest estimates that we know
while HIV one went on to cause AIDS a
pandemic panic has occurred we know that
there are about 37 million people
infected with HIV one out of which only
2 million people have HIV 2 infection so
most of the scientists were focusing on
HIV 1 under the spotlight they were
finding new drugs they were designing
new drugs they were actually studying
the replication cycle of the virus and
trying to fight each and every way this
stop is devastating pandemic that we
know and while doing so being humans and
focusing on the larger picture we let
HIV to slowly slip from under our radar
into oblivion and that’s why we call it
the Forgotten virus we don’t really know
much about that bars the lifecycle or
the treatment options for retroviruses
is quite simple forget this gibberish
and technical jargon ok subtle
microbiology class I’m going to simplify
it you can either block the integration
between the virus and the cells so we
essentially block the entry of the virus
using the fusion inhibitors you can
inhibit a very important step in the
retroviral cycle which is the reverse
transcription
now the retroviruses are extremely
intelligent group of viruses why because
they have RNA instead of DNA as their
genetic material so to be able to
integrate into our own cellular DNA
genome they have to be transcribed they
have to change the RNA into DNA so if
you block this step then there’s not
going to be any more DNA there is no
integration another option is to use
integrase inhibitors when you inhibit
the enzyme that will mediate the viral
DNA integration into our
n/a and the last option and my area of
expertise is when you use maturation
inhibitors maturation is a very
important step in the world life cycle
which will process the viral protein
into more mature forms the virus
structures become more organized and can
infect other cells so if you block this
step you will have what we call immature
variants which means that they’re
incapable of causing infection and they
simply die out to make it simpler for
you to understand how an anti HIV drug
would work I chosen one of the enzymes
that causes the maturation of the virus
it’s called the viral protease this
helmet cool-looking structure is
actually the viral enzyme itself this is
how it looks like and if we imagine that
this is the viral premature proteins and
this is where I’ve exerted all my
artistic abilities it took me two hours
to prepare this demonstration for you so
please bear with me the enzyme is going
to bite to these proteins and it’s going
to process them to more mature form and
the virus is going to be more structured
and able to affect more and more cells
now when you lose a drug to inhibit this
enzyme the drug is going to bind to the
active site of the enzyme which means
that the premature plural proteins are
not able anymore to bind to the viral
enzyme so what is the problem you may
ask the problem results because
retroviruses are intelligent viruses and
each time there is a reverse
transcription of the viral genome new
mutations happen actually at least five
mutations occur at each and every
replication cycle each cell is able to
produce 100,000 variants calculate you
do the math so these mutation will
happen in sites where the inhibitor
actually binds and this will lead to the
inhibitor weakly interacting with the
viral enzyme up to a point where it can
no longer hold its place inhibiting the
mature the viral processing of the
proteins and the bar is going to
continue one processing those proteins
even though they still have these
mutations and that’s why well that’s
what we really call the viral
adaptive fitness we know for sure that
there’s a 40 to 60% difference in the
genetic sequence between the two viruses
as an example I brought here the viral
protease okay the one that matures the
enzyme the viral proteins we know now
that there’s a big directed sequence
between the two viruses some amino acids
which are of course the building blocks
of proteins are actually present in HIV
– that are associated with those
treatment mutations that I showed you in
the previous slide so anyone in the
right mind would know that okay we have
to question whether the drugs used to
treat HIV one can actually block HIV –
and this what we were set out to do
we’ve analyzed the drugs bear in mind
that these drugs have been designed with
HIV one they’ve never been tested on HIV
– and to our surprise we found out that
almost 50% of the drugs that we use to
treat HIV – infected patients are
actually have lower efficacy they are
much much weaker and other drugs so this
brings into question are the type of
methods that we use clinical centers
where aids is tanned emic do not
differentiate between hiv-1 and hiv-2
infections it’s simple patient has AIDS
give them the standard drugs that we
know nobody test them okay so it is
extremely important and I’m I feel that
this is a bit late that we’re only
realizing this now that 50% of the drugs
we use and infected patients are not as
effective as the others and the biggest
problem is that while we have been busy
with HIV one and we thought what is to
millions competitor – seven million
infected by HIV one HIV – has been
spreading well beyond the geographical
confines of western Africa with recent
statistics showing that the incidence of
HIV 2 infection has spread all the way
to Europe especially in Portugal in
Spain and also France for that matter
it’s also spent as far as India and Asia
even Japan and Latin American area at
the incidence I can guarantee you it’s
increasing it’s much more than the 2
million that the
actually believe at least four to five
millions hiv-infected so we need to
exactly characterize the drugs we need
to tailor the treatment for HIV to
infected patients one more interesting
thing I’d like to show share with you
about HIV too is when I started working
at the lab of Professor II of torture
for my PhD studies I came across an
article that was published in 1997 now
in this article it was a purely clinical
article and it showed that there are
some patients were actually infected by
both viruses okay the interesting thing
was that those patients were infected
with two viruses hiv-1 and hiv-2 we call
them the dual infection actually did
better than those who are infected with
HIV one they lived longer they didn’t
develop symptoms of AIDS they were much
better off with this dual infection so
cool I thought I never gave it any more
attention until one day I was reading
this sentence by Shakespeare I don’t
know why because I never read usually
but I came across this fighting fire
with fire phrase and I thought to myself
okay let’s try this I was starting my
work at the lab I had cool pipettes I
had access to very expensive cool
instruments and frankly you put a
clinician in a lab full of toys would
expect him to do naturally expect him to
start playing and that’s what I did I
tried to infect both cells with viruses
at the same time and see what happens
and during that time I had a really
really passionate enthusiastic student
who’s ready to play along and so when
you carried out her experiment we showed
that the dual infection will affect
cells with two verses at the same time
has decreased the HIV ones infectivity
by 67% and so cool I thought this is
turning into one serious game we’re
playing here so moving on I said what’s
going to happen if we do this super
infection where we infect the cells
first with HIV – and then HIV
one and to our surprise this has
decreased the infectivity of hiv-1 to
almost complete illustration of hiv-1
infection now things were getting
serious I was ecstatic we were really
happy and even did the victory dance I
remember in the lab I was that happy and
now we thought we started to play
catch-up with the virus with playing
hide-and-seek we’re trying to find what
is it in HIV – that causes this decrease
in affectivity of HIV 1 and the question
was simple the answer was not we were
trying to dissect each and every single
element of the virus to find out what
was responsible until a couple of months
ago where we are quite positive that
we’ve identified the factor that was
responsible for this decrease in its
activity so the message I want you all
to take home with you today or tonight
is that it was our wrong assumptions
about that the drugs used for HIV one
can cure HIV to infected patients that
have led to an increase in the HIV –
incidence if you continue these
practices I’m pretty sure we’re going to
have an epidemic that as dangerous as
the one that was caused by HIV one of
course the dual infectivity it’s the
preliminary results that we’re reaching
now but we’re quite positive that this
might all the key the designing the
drugs to treat HIV and AIDS for that
matter is quite a generic form you
InDesign inhibitors that bind to the
enzyme until mutations happen so this
could be fighting a losing battle with
the viral enzymes and proteins so could
this hold the answer to treating AIDS
I really really hope so of course we
have to carry on more experiments and
I’ll be happy to let you know as soon as
you reach the conclusive results and
finally the brightest mind of our time
once said that he doesn’t have any
special talents
he’s only simply curious of course that
was Albert Einstein I’ve had this idea
when I was laying on my couch reading
Shakespeare I’ve never had any
training in a lab or molecular biology
for that matter I simply had an idea and
I try to pursue so my message to you is
that if you have an idea or an impulse
please
follow it a productive impulse that is
you might never know what it’s going to
lead you into of course you will not get
that far without the help of a dedicated
team with people who can help you all
the time students who are enthusiastic
and of course a supervisor who would
hold your hand and of course sign your
monthly checks thank you very much for
attention [Applause]
tonight for two reasons one is that
you’re such a lovely audience and I’m
I’ve got the pleasure of meeting most of
you in person and two is because
probably my parents are watching this
right now and they did wondering for so
long what on earth why we doing hungry
for all these years so it is time that
they actually know we’re talking today
about HIV the story started about a
century ago this is where a simian virus
a virus it was only infecting primates
such as monkeys were affecting the
chimpanzees somewhere in Africa now in
multiple types of the simian virus have
infected the chimpanzee monkey
recombination happened and this means
that there was an exchange between
genetic material between the viruses and
after this recombination a new virus was
born and that was able to cross infect
other species such as humans this was of
course the HIV one that causes the
devastating disease that we know as AIDS
or acquired immunodeficiency syndrome
around that time the recombination of
the simian virus is in another type of
monkey which is called the mangabey
monkey present in western Africa and
some parts of Central Africa as a result
in the evolvement of the HIV type two
there I’m quite sure that not many of
you know so Hance is going to be my
topic there’s a great difference between
the two viruses yes they have evolved
from the same ancestor which is a simian
virus however we know that there’s a
great genetic difference between the two
viruses there are about forty to sixty
percent difference in the genetic
sequence between the two viruses this
has resulted in genes being present in
one and not the other the difference in
the genetic sequence has led to
variability in the clinical spectrum
between the two viruses while HIV one is
regarded as the most aggressive type of
the two viruses it tends to cause AIDS
which is the disease much much faster
than HIV – if you’re infected by HIV one
you will develop AIDS within five to ten
years
whereas if you infected with HIV – it
tends to integrate into chromosomal DNA
for quite a longer period 10 15 20 years
even without treatment and most
importantly since the HIV – has evolved
from mangaboos monkeys in western Africa
we thought that the number of patients
infected is quite limited let’s say
about one to two million are going to
the roughest estimates that we know
while HIV one went on to cause AIDS a
pandemic panic has occurred we know that
there are about 37 million people
infected with HIV one out of which only
2 million people have HIV 2 infection so
most of the scientists were focusing on
HIV 1 under the spotlight they were
finding new drugs they were designing
new drugs they were actually studying
the replication cycle of the virus and
trying to fight each and every way this
stop is devastating pandemic that we
know and while doing so being humans and
focusing on the larger picture we let
HIV to slowly slip from under our radar
into oblivion and that’s why we call it
the Forgotten virus we don’t really know
much about that bars the lifecycle or
the treatment options for retroviruses
is quite simple forget this gibberish
and technical jargon ok subtle
microbiology class I’m going to simplify
it you can either block the integration
between the virus and the cells so we
essentially block the entry of the virus
using the fusion inhibitors you can
inhibit a very important step in the
retroviral cycle which is the reverse
transcription
now the retroviruses are extremely
intelligent group of viruses why because
they have RNA instead of DNA as their
genetic material so to be able to
integrate into our own cellular DNA
genome they have to be transcribed they
have to change the RNA into DNA so if
you block this step then there’s not
going to be any more DNA there is no
integration another option is to use
integrase inhibitors when you inhibit
the enzyme that will mediate the viral
DNA integration into our
n/a and the last option and my area of
expertise is when you use maturation
inhibitors maturation is a very
important step in the world life cycle
which will process the viral protein
into more mature forms the virus
structures become more organized and can
infect other cells so if you block this
step you will have what we call immature
variants which means that they’re
incapable of causing infection and they
simply die out to make it simpler for
you to understand how an anti HIV drug
would work I chosen one of the enzymes
that causes the maturation of the virus
it’s called the viral protease this
helmet cool-looking structure is
actually the viral enzyme itself this is
how it looks like and if we imagine that
this is the viral premature proteins and
this is where I’ve exerted all my
artistic abilities it took me two hours
to prepare this demonstration for you so
please bear with me the enzyme is going
to bite to these proteins and it’s going
to process them to more mature form and
the virus is going to be more structured
and able to affect more and more cells
now when you lose a drug to inhibit this
enzyme the drug is going to bind to the
active site of the enzyme which means
that the premature plural proteins are
not able anymore to bind to the viral
enzyme so what is the problem you may
ask the problem results because
retroviruses are intelligent viruses and
each time there is a reverse
transcription of the viral genome new
mutations happen actually at least five
mutations occur at each and every
replication cycle each cell is able to
produce 100,000 variants calculate you
do the math so these mutation will
happen in sites where the inhibitor
actually binds and this will lead to the
inhibitor weakly interacting with the
viral enzyme up to a point where it can
no longer hold its place inhibiting the
mature the viral processing of the
proteins and the bar is going to
continue one processing those proteins
even though they still have these
mutations and that’s why well that’s
what we really call the viral
adaptive fitness we know for sure that
there’s a 40 to 60% difference in the
genetic sequence between the two viruses
as an example I brought here the viral
protease okay the one that matures the
enzyme the viral proteins we know now
that there’s a big directed sequence
between the two viruses some amino acids
which are of course the building blocks
of proteins are actually present in HIV
– that are associated with those
treatment mutations that I showed you in
the previous slide so anyone in the
right mind would know that okay we have
to question whether the drugs used to
treat HIV one can actually block HIV –
and this what we were set out to do
we’ve analyzed the drugs bear in mind
that these drugs have been designed with
HIV one they’ve never been tested on HIV
– and to our surprise we found out that
almost 50% of the drugs that we use to
treat HIV – infected patients are
actually have lower efficacy they are
much much weaker and other drugs so this
brings into question are the type of
methods that we use clinical centers
where aids is tanned emic do not
differentiate between hiv-1 and hiv-2
infections it’s simple patient has AIDS
give them the standard drugs that we
know nobody test them okay so it is
extremely important and I’m I feel that
this is a bit late that we’re only
realizing this now that 50% of the drugs
we use and infected patients are not as
effective as the others and the biggest
problem is that while we have been busy
with HIV one and we thought what is to
millions competitor – seven million
infected by HIV one HIV – has been
spreading well beyond the geographical
confines of western Africa with recent
statistics showing that the incidence of
HIV 2 infection has spread all the way
to Europe especially in Portugal in
Spain and also France for that matter
it’s also spent as far as India and Asia
even Japan and Latin American area at
the incidence I can guarantee you it’s
increasing it’s much more than the 2
million that the
actually believe at least four to five
millions hiv-infected so we need to
exactly characterize the drugs we need
to tailor the treatment for HIV to
infected patients one more interesting
thing I’d like to show share with you
about HIV too is when I started working
at the lab of Professor II of torture
for my PhD studies I came across an
article that was published in 1997 now
in this article it was a purely clinical
article and it showed that there are
some patients were actually infected by
both viruses okay the interesting thing
was that those patients were infected
with two viruses hiv-1 and hiv-2 we call
them the dual infection actually did
better than those who are infected with
HIV one they lived longer they didn’t
develop symptoms of AIDS they were much
better off with this dual infection so
cool I thought I never gave it any more
attention until one day I was reading
this sentence by Shakespeare I don’t
know why because I never read usually
but I came across this fighting fire
with fire phrase and I thought to myself
okay let’s try this I was starting my
work at the lab I had cool pipettes I
had access to very expensive cool
instruments and frankly you put a
clinician in a lab full of toys would
expect him to do naturally expect him to
start playing and that’s what I did I
tried to infect both cells with viruses
at the same time and see what happens
and during that time I had a really
really passionate enthusiastic student
who’s ready to play along and so when
you carried out her experiment we showed
that the dual infection will affect
cells with two verses at the same time
has decreased the HIV ones infectivity
by 67% and so cool I thought this is
turning into one serious game we’re
playing here so moving on I said what’s
going to happen if we do this super
infection where we infect the cells
first with HIV – and then HIV
one and to our surprise this has
decreased the infectivity of hiv-1 to
almost complete illustration of hiv-1
infection now things were getting
serious I was ecstatic we were really
happy and even did the victory dance I
remember in the lab I was that happy and
now we thought we started to play
catch-up with the virus with playing
hide-and-seek we’re trying to find what
is it in HIV – that causes this decrease
in affectivity of HIV 1 and the question
was simple the answer was not we were
trying to dissect each and every single
element of the virus to find out what
was responsible until a couple of months
ago where we are quite positive that
we’ve identified the factor that was
responsible for this decrease in its
activity so the message I want you all
to take home with you today or tonight
is that it was our wrong assumptions
about that the drugs used for HIV one
can cure HIV to infected patients that
have led to an increase in the HIV –
incidence if you continue these
practices I’m pretty sure we’re going to
have an epidemic that as dangerous as
the one that was caused by HIV one of
course the dual infectivity it’s the
preliminary results that we’re reaching
now but we’re quite positive that this
might all the key the designing the
drugs to treat HIV and AIDS for that
matter is quite a generic form you
InDesign inhibitors that bind to the
enzyme until mutations happen so this
could be fighting a losing battle with
the viral enzymes and proteins so could
this hold the answer to treating AIDS
I really really hope so of course we
have to carry on more experiments and
I’ll be happy to let you know as soon as
you reach the conclusive results and
finally the brightest mind of our time
once said that he doesn’t have any
special talents
he’s only simply curious of course that
was Albert Einstein I’ve had this idea
when I was laying on my couch reading
Shakespeare I’ve never had any
training in a lab or molecular biology
for that matter I simply had an idea and
I try to pursue so my message to you is
that if you have an idea or an impulse
please
follow it a productive impulse that is
you might never know what it’s going to
lead you into of course you will not get
that far without the help of a dedicated
team with people who can help you all
the time students who are enthusiastic
and of course a supervisor who would
hold your hand and of course sign your
monthly checks thank you very much for
attention [Applause]
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