Transcript Mon, Sept 23

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Overall Score: ______________
Date
Mon, Sept 16
Disease
Ebola
Mon, Sept 23
HIV
Mon, Sept 30
ERVs
Mon, Oct 7
Influenza
Week of Oct 14
Mon, Oct 21
MIDTERM
Cholera
Mon, Oct 28
Smallpox
Mon, Nov 4
MRSA
Mon, Nov 11
Malaria
Mon, Nov 18
Cancer
Mon, Nov 25
Polio
Mon, Dec 2
Prions
Papers
Leroy et al. 2004
Walsh, Biek and Real, 2005
The International HIV
Controllers Study 2010
Worobey et al. 2008
Van Manen et al. 2008
Sawyer et al. 2006
Tumpey et al. 2005
Yu et al. 2008
NO READINGS
Gagneux et al. 2006
Namouchi et al. 2012
Gani and Leech 2001
Stitelaar et al. 2006
Price et al 2012
Harris et al. 2010
Tanabe et al. 2010
Miotto et al. 2013
Siddle et al. 2007
Murchison et al. 2012
Kew et al. 2002
Coleman et al. 2008
Mead et al. 2003
Mead et al. 2009
Presenter
Ahearn
Bala
Bennett
Sadhana
Barnhart
O'Connor
Benson
Dillard
Gannage
Greenberg
Derana
Mary
Josephine
Sarah
Catherine
Daniel
Greene
Lambert
Le
Liu
Meltzer
Mukhi
Muniz
Peric
Ryan
Brianna
Mimi
David
Jourdan
Ashna
Richard
Andrew
SARS
• Severe acute respiratory syndrome (SARS) is a viral
respiratory illness caused by a coronavirus, called
SARS-associated coronavirus (SARS-CoV).
• SARS was first reported in Hong Kong in November
2002. The illness spread to more than 37 countries in
North America, South America, Europe, and Asia before
the SARS global outbreak of 2003 was contained.
• 8,422 confirmed cases and 916 deaths worldwide.
• Since 2004, there have not been any known cases of
SARS reported anywhere in the world.
CDC, Wikipedia
Coronavirus
• Coronaviruses are positive-strand,
enveloped RNA virus known to cause
enteric and respiratory infections in many
animals, including the common cold.
• The SARS coronavirus seen in electron
microscopy of respiratory secretions and
affected tissue from SARS patients.
• April 2003: Genome sequenced, and
Koch’s postulates satisfied using
macaques.
Diagnosis
• Fever > 38°C (= 100.4°F)
• Contact with someone diagnosed with
SARS or travel to affected region
• Chest X-ray
• Molecular tests
– ELISA (only 21 days after onset)
– Immunofluorescence (expensive)
– PCR (false negatives)
Treatment
• Quaranteen
• Antipyretics, O2 and ventilation support
• Vaccine announced in December 2004
Epidemiology
• Appears to have originated in Guangdon
Province, China in November 2002.
• February 2003 an American businessman
became sick and died in Hanoi; some of
his medical staff also become sick.
• Hong Kong “Hotel
M(etropole)” index
case, mainland Chinese
doctor who infected 16
other guests.
Middle East Respiratory
Syndrome (MERS)
• Since 22 April, 2012 there have been 108 cases and 50
fatalities. Death due to pneumonia and acute renal
failure.
• More than half these cases were in Saudi Arabia, and
more than 80% were male.
• Person-to-person transmission is very low.
• On 15 Sept, 2012 a PCR test was reported.
• Caused by MERS-CoV, with very high similarity to both
bat and pig CoVs.
• Ribavirin + interferon improves outcome in infected
rhesus monkey (Sept 8, 2013)
Wikipedia, CDC
Sources
•
•
•
•
CDC
NIH
WHO
Wikipedia
“Comparative Full-Length Genome
Sequence Analysis of 14 SARS
Coronavirus Isolates and Common
Mutations Associated with Putative
Origins of Infection”
YiJun Ruan et al.
The Lancet 361:1779 - 1785
Introduction
• SARS first identified in November 2002; spread
worldwide by April 2003
• Putative cause is a new coronavirus:
– Oropharyngeal specimens from patients induced a
pathology in cell culture
– Coronovirus-like particles observed
– PCR revealed coronavirus-like sequences
– PCR positive in clinical isolates
– Coronavirus antibodies detected in SARS patients
Method
• Respiratory samples from patients
• Confirm infectivity in cell culture (Vero
cells)
• PCR to verify presence of SARS-CoV
• Synthesize cDNA from total RNA
• Sequence resulting cDNA
SARS-CoV Genome
9479, 9854,
19838, 27243
8559
19084
9404, 17564, 22222, 27827
2601
7919, 19064
Bats Are Natural Reservoirs of
SARS-Like Coronaviruses
Li et al. (2005)
Science 310:676 - 679
Introduction and Methods
• SARS emerged in 2002 or 2003 in
southern China, but the origin of the
causative agent (SARS-CoV) remains
unknown.
• Sampled 408 bats from nine species, six
genera and three families from four
locations in China, and screened these for
SARS antibodies and with PCR.
SARS-CoV widespread in three
Rhinolophus species
Figure 1 – Alignment of whole genome sequences for isolates
from Rhinolophus (Rp3), human (Tor2) and palm civet (SZ3).
Figure 2 – Phylogenetic relationship among corona viruses from humans
(Tor2), palm civet (SZ3), Rhinolophus bats (Rp3) and other sources. Based
on amino acid sequence data from P1 (upper) and S (lower) proteins.
(Protein N)
(Protein ORF10’)
(Protein S1)
Figure 3 – Phylogenetic relationship among SARS corona viruses at
three loci, strongly suggesting the action of genetic recombination.
Implications
• SARS-CoV more likely to be derived from
an endemic bat virus. (Civet unlikely
source because when infected, civets
show human-like symptoms, which mean
that in nature these individuals are unlikely
to survive.)
• SARS-CoV capable of genetic
recombination, which may account for its
ability to jump between host species.