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MERS-CoV

CMMB 421: Virology Seminar
by

Nicky Nazareth

on 4 December 2013

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Transcript of MERS-CoV

MERS-CoV

By: Nicole Nazareth
Middle East Respiratory Syndrome Coronavirus
Coronavirus
Coronaviridae broken into four genera
Alpha-, Beta-, Delta- and Gammacoronavirus

Largest of all RNA viruses, enveloped positive single stranded helical virus

Undergoes discontinuous negative strand transcription
RNA-RNA recombination leads to high rate of mutation (high adaption)

Spike protein mediates receptor attachment
Reported and analyzed the entire genome of HCoV-EMC/2012 through Sanger sequencing and 454 deep sequencing

Showed two large partially overlapping replicase open reading frames ORF1a and ORF1b, as well as nine downstream ORFs

Both 5' and 3' ends appeared to be truncated

First human coronavirus to be found in betacoronavirus linage C

Genome fragments showed the highest similarity to BtCoV-HKU4 and HKU5; both these betacoronaviruses are circulating in bats
Transmission, Evolution and Origin
What is MERS-CoV
Betacoronavirus that first appeared in June 2012

Name originates from its link to four Middle Eastern countries: Saudi Arabia, Jordan, Qatar and the United Arab Emirates
Since first appearance has been documented in: UK, France, Italy and Tunisia

Causes acute respiratory distress syndrome and multiple organ dysfunction syndrome: initial symptoms seen are fever, cough and experience of being short of breath

Mortality rate of almost 50%

Is compared to the SARS-CoV scare of 2002/2003
Apoptosis in Epithelial Cells
MERS-CoV Genome
Compared the infectivity of SARS-CoV to MERS-CoV

MERS-CoV showed visible cytopathic effect much quicker then SARS-CoV

CPE due to caspase dependent apoptosis mechanism

Capable of infecting via the apical or basolateral cell domains, therefore may work via blood borne dissemination
Used full genome deep sequencing based on 21 case samples

Most changes found in the last third of the genome
This area responsible for important accessory proteins and the receptor-binding spike protein

Recent MERS-CoV encoded S proteins differently then how the original HCoV-EMC/2012 that was studied did

Showed that there are three distinct genotypes of MERS-CoV infecting individuals
Means there are rapid changes that are occurring
References
1) Boheemen, S. Van, Graaf, M. De, & Lauber, C. (2012). Syndrome in Humans Genomic Characterization of a Newly Discovered Coronavirus. doi:10.1128/mBio.00473-12.Editor

2) Tao, X., Hill, T.E., Morimoto, C., Peters, C.J., Ksiazek, T. G., & Tseng, C-T. K. (2013). Bilateral entry and release of Middle East respiratory syndrome coronavirus induces profound apoptosis of human bronchial epithelial cells.
Journal of virology
, 87(17), 9953-8, doi:10.1128/JVI.01562-13

3) Cotten, M., Watson, S.J., Kellam, P., Al-Rabeeah, A. a, Makhdoom, H. Q., Assiri, A., ...Memish, Z. a. (2013). Transmission and evolution of the Middle East respiratory syndrome coronavirus in Saudi Arabia: A descriptive genomic study.
Lancet
, 6736(13), 1-10. doi:10/1016/S0140-6736(13)61887-5

4) CDC - Coronavirus - Middle East Respiratory Syndrome - MERS-CoV. http://www.cdc.gov/coronavirus/mers/. November 27th 2013.
Questions?
Figure 1. Modified from (1), shows the full genome of HCoV-EMC/2012
Figure 2. Modified from (2), shows the one step growth curve of SARS-CoV and MERS-CoV by using an MOI of 3
Figure 3. Modified from (2), Shows mock, SARS-CoV infected and MERS-CoV infected cells. MERS-CoV varies from SARS-CoV in that it displays the presence of typical apoptotic bodies and CCP3 (bright green) in the cytoplasm.
Figure 4. Modified from (2). Displays how MERS-CoV has the ability to infect via both the apical and basolateral domains, unlike SARS-CoV which can only infect through the apical domain.
Figure 5. Modified from (3). Transmission network for all Al-Hasa MERS-CoV samples used in this study. Light blue nodes show a statistically probable transmission linkage whereas green nodes cannot be linked by direct transmission.
Full transcript