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- Dr. Raphaela Goldbach-Mansky
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13. Signaling for the interferon family of receptors and ligands and clinical implications
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14. Interferons as antivirals: translating basic research into clinical application
- Prof. Eleanor N. Fish
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Printable Handouts
Navigable Slide Index
- Introduction
- Health concerns in the 20th and 21st centuries
- Different viral infections worldwide
- Current treatments
- Drug development considerations for antivirals
- Innate immune response
- Different pathogen recognition receptors
- IFN influences on immune response
- High conservation degree in IFNalpha subtypes
- IFN subtypes exhibit variable antiviral potency
- Type I IFN signaling
- Global outbreak of SARS
- Why so virulent?
- A mouse model of SARS CoV
- Type I IFN expression profile in infected mice
- IFN-beta protects A/J mice from MHV-1 infection
- Inhibition of SARS CoV by IFN
- Representative chest X-rays in SARS patients
- Interferon effect on lung pathology
- O2 saturation over time
- Interferon prevents HIV spread
- IFN inhibits HIV infection
- Coxsackievirus B3
- IFN gene expression in CVB3 infected mice
- IFN-beta in patients with cardiomyopathy
- Influenza
- Human lung organ model for influenza infection
- IFN alfacon-1 inhibits H5N1 replication in lung
- Swain flu
- IFN treatment inhibits A/WSN/33 H1N1 infection
- IFN-alpha treatment inhibits influenza replication
- IFN inhibits influenza replication
- Post infection IFN alfacon-1 inhibits influenza
- IFN inhibits pandemic H1N1 replication
- A pilot study
- IFNs exhibit different affinities for IFNAR
- 3 amino acid clusters residues influence activity
- IFN alfacon-1
- IFN-alpha-2 interaction with receptor
- Receptor affinity
- In silico modeling
- Strategy for design of nonpeptide mimetics
- Acknowledgements
Topics Covered
- Emerging and re-emerging virus infections globally
- Time lag before a new vaccine is available during a pandemic
- Antivirals that are pathogen specific lead to viral resistance
- Broad spectrum antivirals needed
- Interferons -alpha -beta are produced in response to all virus infections
- Every cell/tissue will respond to interferon
- Widespread application for all virus infections
- Update interview: Consider route of administration for most effective outcome
- Update interview: Prophylactic treatment in specific settings
Links
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Therapeutic Areas:
Talk Citation
Fish, E.N. (2021, February 20). Interferons as antivirals: translating basic research into clinical application [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 12, 2024, from https://doi.org/10.69645/YESW7249.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Eleanor N. Fish has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Update Available
The speaker addresses developments since the publication of the original talk. We recommend listening to the associated update as well as the lecture.
- Full lecture Duration: 45:07 min
- Update Interview Duration: 12:11 min
Interferons as antivirals: translating basic research into clinical application
A selection of talks on Clinical Practice
Transcript
Please wait while the transcript is being prepared...
0:00
I'm Eleanor Fish, a senior scientist at the Toronto General Research Institute
University Health Network in Toronto,
and a professor in the department of immunology at the University of Toronto.
This presentation, as the title suggests,
will describe how interferons are broad-spectrum antivirals,
and hopefully provide some insights into how we can
translate basic research findings into clinical application.
0:28
In the 20th century a major health concern surrounded bacterial infections.
Fortunately, antibiotics allowed us to deal with those bacterial infections.
Now, in the 21st century,
I would argue that our major concern surrounds viruses.
0:48
If we consider HIV, currently
there are anywhere between 35 and 42 million people living with AIDS around the globe.
Notably (where I've taken this particular photograph)
in Kenya, there are currently two million people suffering with AIDS and
concomitantly about anywhere from 5 to 10 percent of them also infected with TB.
Next, if we look at hepatitis (hepatitis B virus infection),
two billion people are infected around the globe, and
350 million chronically each year.
In terms of HCV (hepatitis C virus),
we know there are about 170 million people infected,
3 to 4 million each year being newly infected.
West Nile virus, as its name suggests, originated in the West Nile.
Again, a virus infection which has now come to North America, and we are
acutely aware of the neurological sequelae that accompany this virus infection,
there are no current antiviral therapies for West Nile virus.
With hepatitis C virus infection,
we have interferon treatment currently, for hepatitis B virus there is a vaccine,
with HIV, although we are looking for a vaccine there's not one available,
and currently people who are chronically infected with HIV carry on thanks to
the highly active antiretroviral therapies, HAART treatment.
Lassa fever next, this is another virus infection
(perhaps one that we're not familiar with in the western world)
affecting 500,000 individuals per year alone in West Africa.
There's no treatment for this particular virus infection other than supportive care.
In the late 2000s (I think around about 2007)
there was an enterovirus outbreak in China where thousands of children were infected,
again there was no treatment just supportive care, and the only reason why this
didn't hit the headlines was because of the earthquake in China.
Dengue virus is another virus which is emerging as a serious global threat.
There are approximately 50 million cases per year,
and again, no treatment beyond supportive care.
If we look at poliovirus,
you might argue poliovirus has
vaccines against it and yet it is endemic in 2011 in Afghanistan,
in India, in Nigeria, in Pakistan and most recently in Sierra Leone.
Again, there is no treatment for acute infection.
Ebola virus is another virus infection which does not raise any alerts in the western world,
but has 50 to 90 percent fatality rates in the African continent for those infected.
If we look at influenza A virus,
we're all becoming acutely aware of the potential for pandemics.
This is because of the most recent one,
I'll also draw your attention to
smallpox virus in the bottom left-hand corner of this particular slide.
Again, you might argue that this is not a concern because
we've eradicated smallpox, and yet we know that
there are stocks of smallpox virus that are not accounted
for around the globe, so that those of us in our 50s and 60s who
were vaccinated are no longer protected from smallpox virus infection, and there are
generations of young people who have never been vaccinated and are completely vulnerable.
Notably, smallpox is one of those viruses that is being weaponized, and
again, there is no treatment for smallpox.
Rift Valley fever virus, again
perhaps not of concern in the western world,
and yet a serious virus infection in Africa, specifically in Kenya.
The point is with each of those viruses
(which you may argue are not of concern to those of us in the 'first world'),
the reality is that now with travel around the globe
these viruses can emerge anywhere around the globe, and should be of concern to all of us.
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