Transcript Lecture 31 Emerging viruses - University of Maryland

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
Myxomatosis: a classic tale of
an emerging virus
• For more info, go to:
http://www.burrill.demon.co.uk/meddoc
/myxo.html
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 couldn’t be eradicated by hunting or poisoning
• Something else had to be done
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
The Plan
• 1919: first suggestion to use Myxoma
virus to control rabbits in Australia.
• 1950: Myxomatosis successfully released
among Australian rabbits.
• Initial mortality rates >90%.
• Best spread by mosquitoes in summer.
• Epidemic continued for 4 or so years with
high mortality rates
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 didn’t 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.
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.
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.
Constantly emerging viruses
• Influenza
• Coronaviruses.
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 rates…high 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.
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
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.
Coronaviruses.
• For more information, see http://wwwmicro.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.
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!
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.
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.
Organization of the SARS-CoV genome
SARS-CoV Viral Particle
Evolutionarily, SARS-CoV is in a
class by itself
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.
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.
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.