Lecture 32 Emerging viruses

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Lecture 32 Emerging viruses

• Definition viruses that are in the process of
  adapting to a new host and vice versa.
• Though emerging viruses tend to be at first
  highly virulent, virus and host co-evolutionary
  processes tend to converge to less virulent virus
  and more resistant host populations.
• Examples of emerging viruses
• Myxoma virus (Rabbitpox)
• Influenza and Coronaviruses are constantly
  emerging

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Myxomatosis a classic tale of an emerging virus

• For more info, go to http//www.burrill.demon.co
  .uk/meddoc/myxo.html

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Background

• In 1759, the European wild rabbit O. cuniculus
  was introduced into Australia by Thomas Austin
  for sport hunting. Almost all of the rabbits in
  Australia are descendants of the 24 original
  rabbits.
• The rabbit spread rapidly, at a rate of advance
  of about 110 kilometres each year. It now occurs
  over half of Australia.
• The lack of any herbivores capable of competing
  with the rabbit resulted in the decline of many
  species of native wildlife by competing with them
  for food or burrows. This applies particularly to
  the small ground-dwelling mammals of the arid
  lands. This situation was made worse by the lack
  of a large population of predators able to deal
  with this new prey.
• By the mid-20th century, rabbits had denuded the
  landscape
• They couldnt be eradicated by hunting or
  poisoning
• Something else had to be done

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Myxomavirus

• Myxoma virus, a member of the large Poxvirus
  group about 280nm in length.
• Myxomtosis The disease was uncovered in South
  America in 1896 where it had devastating effect
  on the rabbit population there.
• It was found that it was mainly the European
  rabbit (Oryctolagus cuniculus), imported early
  that century, that contracted the disease.
• Myxoma virus is endemic to the local wild rabbit
  population (Sylvilagus brasiliensis) which was
  mostly resistant to the disease and acted at the
  natural reservoir.
• The disease is highly lethal to European rabbits
  with observed mortality rates of greater than
  99.
• Myxoma virus is transmitted by
• Contact infection Discharge from skin and
  ocular lesions.
• Arthropod vectors Mosquitos, fleas, mites,
  ticks.

Myxoma virus particles
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The Plan

• 1919 first suggestion to use Myxoma virus to
  control rabbits in Australia.
• 1950 Myxomatosis successfully released among
  Australian rabbits.
• Initial mortality rates gt90.
• Best spread by mosquitoes in summer.
• Epidemic continued for 4 or so years with high
  mortality rates

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The outcome a paradigm of host/virus
co-evolution

• The virus
• highly virulent forms killed hosts too quickly to
  be effectively spread
• Less virulent forms didnt kill hosts, more virus
  produced over longer time
• Selection for attenuated virus.
• The host
• Susceptible hosts were quickly culled from the
  population
• More resistant hosts lived to reproduce
• ? Selection for resistant rabbits.
• Today myxomatosis in Australia kills only about
  40 of infected rabbits, but rabbit numbers are
  much lower than they would be in the absence of
  this disease.

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Myxomatosis in Europe

• Similar to Australia, rabbits were a major cause
  of damage, particularly to the national forests
  of France.
• 1952 Dr P.F. Armand Delille inoculated two wild
  rabbits at Maillebois in northern France.
• From these two rabbits myxomatosis spread all
  round Europe, including Britain and Ireland, and
  as far a field as North Africa.
• The main means of transmission of the virus was
  the mosquito as well as the rabbit flea.
• The disease had the same result as in Australia
  the majority of the wild rabbit population of
  Europe was wiped out, including an estimated 90
  of French and British rabbits.

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Myxomatosis in Europe

• Attenuation and genetic resistance has occurred
  in Europe
• Unlike in Australia where the highly attenuated
  strains have replaced the virulent original, in
  Europe the two coexist.
• This is due to a different vector situation where
  the rabbit flea is believed to be the main
  vector, especially in Britain where the variation
  in number of cases of myxomatosis does not vary
  greatly throughout the year.
• Myxomatosis is now an enzootic disease in the
  wild rabbits of Europe, with occasional summer
  epizootics, particularly in France.

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Constantly emerging viruses

• Influenza
• Coronaviruses.

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Influenza

• All aspects of Influenza A conspire for it to be
  a constantly emerging virus
• Genome 9 segments of () strand RNA.
• Segments Allows for large scale recombinationv
  genetic shift.
• RNA genome RDRPs have high error rateshigh
  rates of mutation genetic drift.
• Ecology reservoir is migrating waterfowl.
  Alternate hosts are almost all mammals.
  Impossible to eradicate.
• Anthropology Crowded, agrarian culture in
  Southeast China provides the ideal environment
  for exchange of virus variants between hosts.
• Technology high mobility of post 18th century
  humans ensures efficient and rapid dissemination
  of new virus variants.

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The result

• Yearly epidemics due to genetic drift.
• Virus and host populations evolve toward benign
  relationship
• Periodic pandemics due to genetic shift
• Highly virulent virus released on an
  immunologically naïve population
• Both host and virus co-selected
• And the cycle continues

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Control

• The WHO monitors Influenza subtypes in Southeast
  Asia
• They have to guess which ones will become the
  most prevalent
• Use these to design the vaccine for 2 years
  later.
• It is a hit or miss process.

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Coronaviruses.

• For more information, see http//www-micro.msb.le
  .ac.uk/3035/Coronaviruses.html
• Human CoV cause 30 of common colds.
• Other animal coronaviruses can cause more
  pathogenic disease, e.g.
• Porcine Epidemic Diarrhea Virus
• Mouse Heptitis Virus
• Avian Infectious Bronchitis virus
• SARS-CoV a scary emerging virus.

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SARS-CoV

• SARS is a type of viral pneumonia
• Symptoms include fever, dry cough, dyspnea
  (shortness of breath), headache, and hypoxaemia
  (low blood oxygen concentration).
• Typical laboratory findings include lymphopaenia
  (reduced lymphocyte numbers) and mildly elevated
  aminotransferase levels (indicating liver
  damage).
• Death may result from progressive respiratory
  failure due to alveolar damage.
• The typical clinical course of SARS involves an
  improvement in symptoms during the first week of
  infection, followed by a worsening during the
  second week.
• Studies indicate that this worsening may be
  related to patient's immune responses rather than
  uncontrolled viral replication.
• The SARS virus is believed to be spread by
  droplets produced by coughing and sneezing, but
  other routes of infection may also be involved,
  such as faecal contamination, so wash your hands!

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History

• Severe Acute Respiratory Syndrome (SARS) first
  appeared in Guangdong Province, China late in
  2002.
• Its rapid transmission and high rates of
  mortality and morbidity resulted in a significant
  threat to global health by the spring of 2003,
  and the epidemic had significant impacts on the
  public health and economies of locales affected
  by SARS outbreaks.
• The rapid response of the World Health
  Organization is credited with containing this
  contagion by late June of 2003, and only a few
  cases were reported during the winter cold season
  of 2003-2004.

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History

• The severity of this crisis mobilized the
  scientific community as well by March 24, 2003,
  scientists at the CDC and in Hong Kong had
  announced that a new coronavirus had been
  isolated from patients with SARS.
• The sequences from two isolates of SARS CoV were
  published simultaneously on May 1, 2003.

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Organization of the SARS-CoV genome
SARS-CoV Viral Particle
Evolutionarily, SARS-CoV is in a class by itself
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Origins
(Good eatin)

• Coronaviruses with 99 sequence similarity to the
  surface spike protein of human SARS isolates have
  been isolated in Guangdong, China, from
  apparently healthy masked palm civets (Paguma
  larvata), a cat-like mammal closely related to
  the mongoose.
• The palm civet is regarded as a delicacy in
  Guangdong
• It is believed that humans became infected as
  they raised and slaughtered the animals rather
  than by consumption of infected meat.

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Outlook

• Could SARS coronavirus recombine with other human
  coronaviruses to produce an even more deadly
  virus?
• Fortunately, the coronaviruses of which we are
  aware indicate that recombination has not
  occurred between viruses of different groups,
  only within a group, so recombination does not
  seem likely given the distance between the SARS
  virus and HCoV.
• There is considerable experience of development
  of coronavirus vaccines for veterinary purposes
  though not all of it is encouraging.
• On the whole, inactivated coronavirus vaccines
  induce poor protection.

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Outlook

• The spike protein alone can induce immunity, but
  the internal nucleoprotein has also been reported
  to induce protective immunity.
• The WHO has recommended that SARS vaccines be
  developed.
• The quickest and probably safest to develop would
  be an inactivated or subunit vaccine.
• Even if such a vaccine were not fully protective
  against SARS infection, it might still provide
  some protection against life-threatening SARS
  pneumonia.