Nobel Prize in Physiology or Medicine 2020: Discovery of Hepatitis C
virus

Date:
October 5, 2020
Source:
Nobel Foundation
Summary:
The 2020 Nobel Prize in Physiology or Medicine is being awarded
jointly to Harvey J. Alter, Michael Houghton and Charles M. Rice
for the discovery of Hepatitis C virus.



FULL STORY ========================================================================== [Hepatitis C virus | Credit: (c) Kateryna_Kon / stock.adobe.com] Hepatitis
C virus infection medical concept, 3D illustration (stock image).

Credit: (c) Kateryna_Kon / stock.adobe.com [Hepatitis C virus | Credit:
(c) Kateryna_Kon / stock.adobe.com] Hepatitis C virus infection medical concept, 3D illustration (stock image).

Credit: (c) Kateryna_Kon / stock.adobe.com Close The Nobel Assembly at Karolinska Institutet has today decided to award the 2020 Nobel Prize
in Physiology or Medicine jointly to Harvey J. Alter, Michael Houghton
and Charles M. Rice for the discovery of Hepatitis C virus.


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This year's Nobel Prize is awarded to three scientists who have made
a decisive contribution to the fight against blood-borne hepatitis,
a major global health problem that causes cirrhosis and liver cancer in
people around the world.

Harvey J. Alter, Michael Houghton and Charles M. Rice made seminal
discoveries that led to the identification of a novel virus, Hepatitis
C virus. Prior to their work, the discovery of the Hepatitis A and B
viruses had been critical steps forward, but the majority of blood-borne hepatitis cases remained unexplained. The discovery of Hepatitis C virus revealed the cause of the remaining cases of chronic hepatitis and made possible blood tests and new medicines that have saved millions of lives.

Hepatitis -- a global threat to human health Liver inflammation, or
hepatitis, a combination of the Greek words for liver and inflammation, is mainly caused by viral infections, although alcohol abuse, environmental
toxins and autoimmune disease are also important causes. In the 1940's,
it became clear that there are two main types of infectious hepatitis.

The first, named hepatitis A, is transmitted by polluted water or food
and generally has little long-term impact on the patient. The second
type is transmitted through blood and bodily fluids and represents a
much more serious threat since it can lead to a chronic condition, with
the development of cirrhosis and liver cancer. This form of hepatitis
is insidious, as otherwise healthy individuals can be silently infected
for many years before serious complications arise. Blood-borne hepatitis
is associated with significant morbidity and mortality, and causes more
than a million deaths per year world- wide, thus making it a global
health concern on a scale comparable to HIV- infection and tuberculosis.

An unknown infectious agent The key to successful intervention against infectious diseases is to identify the causative agent. In the 1960's,
Baruch Blumberg determined that one form of blood-borne hepatitis
was caused by a virus that became known as Hepatitis B virus, and the
discovery led to the development of diagnostic tests and an effective
vaccine. Blumberg was awarded the Nobel Prize in Physiology or Medicine
in 1976 for this discovery.



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At that time, Harvey J. Alter at the US National Institutes of Health was studying the occurrence of hepatitis in patients who had received blood transfusions. Although blood tests for the newly-discovered Hepatitis
B virus reduced the number of cases of transfusion-related hepatitis,
Alter and colleagues worryingly demonstrated that a large number of
cases remained. Tests for Hepatitis A virus infection were also developed around this time, and it became clear that Hepatitis A was not the cause
of these unexplained cases.

It was a great source of concern that a significant number of those
receiving blood transfusions developed chronic hepatitis due to an unknown infectious agent. Alter and his colleagues showed that blood from these hepatitis patients could transmit the disease to chimpanzees, the only susceptible host besides humans. Subsequent studies also demonstrated that
the unknown infectious agent had the characteristics of a virus. Alter's methodical investigations had in this way defined a new, distinct form of chronic viral hepatitis. The mysterious illness became known as "non-A,
non-B" hepatitis.

Identification of Hepatitis C virus Identification of the novel virus was
now a high priority. All the traditional techniques for virus hunting
were put to use but, in spite of this, the virus eluded isolation
for over a decade. Michael Houghton, working for the pharmaceutical
firm Chiron, undertook the arduous work needed to isolate the genetic
sequence of the virus. Houghton and his co-workers created a collection
of DNA fragments from nucleic acids found in the blood of an infected chimpanzee. The majority of these fragments came from the genome of
the chimpanzee itself, but the researchers predicted that some would be
derived from the unknown virus. On the assumption that antibodies against
the virus would be present in blood taken from hepatitis patients, the investigators used patient sera to identify cloned viral DNA fragments
encoding viral proteins.

Following a comprehensive search, one positive clone was found. Further
work showed that this clone was derived from a novel RNA virus belonging
to the Flavivirus family and it was named Hepatitis C virus. The presence
of antibodies in chronic hepatitis patients strongly implicated this
virus as the missing agent.

The discovery of Hepatitis C virus was decisive; but one essential piece
of the puzzle was missing: could the virus alone cause hepatitis? To
answer this question the scientists had to investigate if the cloned virus
was able to replicate and cause disease. Charles M. Rice, a researcher
at Washington University in St. Louis, along with other groups working
with RNA viruses, noted a previously uncharacterized region in the end
of the Hepatitis C virus genome that they suspected could be important
for virus replication. Rice also observed genetic variations in isolated
virus samples and hypothesized that some of them might hinder virus replication. Through genetic engineering, Rice generated an RNA variant
of Hepatitis C virus that included the newly defined region of the viral
genome and was devoid of the inactivating genetic variations. When this
RNA was injected into the liver of chimpanzees, virus was detected in the
blood and pathological changes resembling those seen in humans with the
chronic disease were observed. This was the final proof that Hepatitis
C virus alone could cause the unexplained cases of transfusion-mediated hepatitis.



========================================================================== Significance of this Nobel Prize-awarded discovery The Nobel Laureates' discovery of Hepatitis C virus is a landmark achievement in the ongoing
battle against viral diseases. Thanks to their discovery, highly
sensitive blood tests for the virus are now available and these have essentially eliminated post-transfusion hepatitis in many parts of the
world, greatly improving global health. Their discovery also allowed
the rapid development of antiviral drugs directed at hepatitis C. For
the first time in history, the disease can now be cured, raising hopes
of eradicating Hepatitis C virus from the world population. To achieve
this goal, international efforts facilitating blood testing and making antiviral drugs available across the globe will be required.

Harvey J. Alter was born in 1935 in New York. He received his medical
degree at the University of Rochester Medical School, and trained in
internal medicine at Strong Memorial Hospital and at the University
Hospitals of Seattle. In 1961, he joined the National Institutes of Health (NIH) as a clinical associate. He spent several years at Georgetown
University before returning to NIH in 1969 to join the Clinical Center's Department of Transfusion Medicine as a senior investigator.

Michael Houghton was born in the United Kingdom. He received his PhD
degree in 1977 from King's College London. He joined G. D. Searle &
Company before moving to Chiron Corporation, Emeryville, California in
1982. He relocated to University of Alberta in 2010 and is currently
a Canada Excellence Research Chair in Virology and the Li Ka Shing
Professor of Virology at the University of Alberta where he is also
Director of the Li Ka Shing Applied Virology Institute.

Charles M. Rice was born in 1952 in Sacramento. He received his PhD
degree in 1981 from the California Institute of Technology where he also trained as a postdoctoral fellow between 1981-1985. He established his
research group at Washington University School of Medicine, St Louis in
1986 and became full Professor in 1995. Since 2001 he has been Professor
at the Rockefeller University, New York. During 2001-2018 he was the
Scientific and Executive Director, Center for the Study of Hepatitis C
at Rockefeller University where he remains active.


========================================================================== Story Source: Materials provided by Nobel_Foundation. Note: Content may
be edited for style and length.


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Link to news story: https://www.sciencedaily.com/releases/2020/10/201005091216.htm

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