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MERS-CoV?EM: Saudi Arabia, Genome Sequencing, Jeddah Outbreak (ProMedMail.org / VDU, April 27 2014, edited): No major changes in critical receptor sites on sampled viruse from curr Outbreaks
[Source: ProMedMail.org, full page: (LINK). Edited.]
Published Date: 2014-04-26 22:35:11 / Subject: PRO/AH/EDR> MERS-CoV - Eastern Mediterranean (42): Saudi Arabia, genome sequencing, Jeddah / Archive Number: 20140426.2432140
MERS-CoV?Eastern Mediterranean (42): Saudi Arabia, Genome Sequencing, Jeddah Outbreak
A ProMED-mail post http://www.promedmail.org / ProMED-mail is a program of the International Society for Infectious Diseases http://www.isid.org / Date: Sat 26 Apr 2014
From: Christian Drosten <drosten@virology-bonn.de> [edited]
Sequence information and comments regarding MERS-Coronavirus (CoV) in Jeddah, Kingdom of Saudi Arabia
Recent public comments have considered the possibility that an increase of the number of cases of MERS-CoV infection as seen in cities including Jeddah, Kingdom of Saudi Arabia (KSA) might be associated with changes in the genome of MERS-CoV enabling more efficient transmission between humans.
My lab is one of several partners currently assisting the KSA Ministry of Health (MOH) in laboratory issues related to MERS-CoV.
We have sequenced near full genomes of 3 viruses from the early phase of the Jeddah outbreak.
The samples were submitted to Jeddah regional laboratory on [3, 5 and 7 Apr 2014], and sent to Germany for external confirmatory testing on [14 Apr 2014] by KSA MOH in Riyadh.
Two of the sequenced viruses were from patients treated in the major public hospital in which most cases of the Jeddah outbreak seem to have occurred.
A 3rd sequence was from another health care facility in the city.
Genome sequences of all 3 viruses are highly similar to each other but not identical, and are highly similar to a large number of known MERS-CoV sequences (consult http://www.virology-bonn.de for a phylogeny; genome overview in Cotten 2014).
There are no genome insertions or deletions suggestive of sudden major changes.
The receptor-binding domain in the spike protein thought to influence the virus's ability to be transmitted or spread is 100 percent identical to the binding site in a large number of known MERS-CoV genome sequences.
Based on genome comparison with other MERS-CoV strains there is no reason to assume that the sequenced viruses from Jeddah have acquired changes increasing their pandemic potential.
As long as the sequences are in the draft stage, we are making them available on our homepage (http://www.virology-bonn.de ) and provide them to the epidemic blog (http://epidemic.bio.ed.ac.uk ).
They will be submitted to GenBank after some curating.
We have sequenced partial spike protein genes from another 25 viruses, showing 100 percent sequence identity with above-mentioned genomes.
However, more sequence information needs to be collected before inferences of transmission patterns can be reached (e.g., new acquisitions of infection, for example from animals or unlinked human communities, versus contingent [? contiguous] hospital-based transmission chains).
Of note, hospital-based transmission of MERS-CoV without evidence of changes in the genome of the involved virus has occurred previously, and has been controlled upon enforcement of infection control measures (Assiri 2013, Cotten 2013).
The samples we tested were dispatched to Germany by KSA MOH, Riyadh, on [14 Apr 2014] in the form of RNA extracts with a request for external confirmatory testing in view of the increasing case count in Jeddah.
29 samples had been tested positive in Jeddah regional laboratory by 2 different RT-PCR assays (the upE and 1A RT-PCR assays developed by my laboratory).
28 of these were confirmed in my lab using an alternative target gene (nucleocapsid) not available in Jeddah regional laboratory, excluding contamination at least after the stage of RNA preparation.
According to personal communications with laboratory staff in Jeddah, internal confirmatory testing (i.e., the re-testing by 1A assay of samples tested positive by upE assay) always involves the generation of a new RNA extract from the original clinical sample. (If this practice is complied with, factual contamination risk at the level of the laboratory is very low.)
In light of some of the recent comments implicating delays in following up on the outbreak it is worth considering the timing and the workload associated with careful testing and internal confirmation done in Jeddah.
It is also worth mentioning that samples were already dispatched from KSA MOH Riyadh to Germany on [14 Apr 2014] -- just about a week after receipt of samples in Jeddah regional laboratory, testing, internal confirmatory testing, and transport to Riyadh.
After dispatch from Riyadh, samples were not successfully delivered through customs in Germany with an administrative process that took 3 days (17 Apr 2014).
The sequencing work in Bonn started only on [22 Apr 2014] for the simple reason that most of the laboratory staff (including myself) have been on Easter holidays. Sequencing of further samples taken at later time points in Jeddah is underway.
Christian Drosten (also on behalf of Victor Corman who did the sequencing)
References:
--
Christian Drosten, Institute of Virology, University of Bonn Medical Centre, Sigmund Freud Str 25, 53105 Bonn, Germany drosten@virology-bonn.de
[ProMED would like to thank Prof. Drosten for sharing this important and valuable information. There have been many rumors circulating pushing the theory that the MERS-CoV circulating in Jeddah has "mutated" with an adaptation for significantly enhanced human-to-human transmission.
These preliminary findings provide scientific evidence that at present the virus has not significantly altered its receptor sites affecting the virus's transmissibility potential.
This sequence evidence rather supports the idea that non-viral factors (e.g., epidemiologic, behavioral, environmental, host, etc.) have led to the recent upsurge in cases.
We look forward to the results on more recent specimens (from the past week or so) to see if there have been significant changes.
We also look forward to results of case control studies on these outbreaks (in Jeddah, Riyadh and the UAE) to further identify the risk factors for transmission in these outbreaks. - Mod.MPP]
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Published Date: 2014-04-26 22:35:11 / Subject: PRO/AH/EDR> MERS-CoV - Eastern Mediterranean (42): Saudi Arabia, genome sequencing, Jeddah / Archive Number: 20140426.2432140
MERS-CoV?Eastern Mediterranean (42): Saudi Arabia, Genome Sequencing, Jeddah Outbreak
A ProMED-mail post http://www.promedmail.org / ProMED-mail is a program of the International Society for Infectious Diseases http://www.isid.org / Date: Sat 26 Apr 2014
From: Christian Drosten <drosten@virology-bonn.de> [edited]
Sequence information and comments regarding MERS-Coronavirus (CoV) in Jeddah, Kingdom of Saudi Arabia
Recent public comments have considered the possibility that an increase of the number of cases of MERS-CoV infection as seen in cities including Jeddah, Kingdom of Saudi Arabia (KSA) might be associated with changes in the genome of MERS-CoV enabling more efficient transmission between humans.
My lab is one of several partners currently assisting the KSA Ministry of Health (MOH) in laboratory issues related to MERS-CoV.
We have sequenced near full genomes of 3 viruses from the early phase of the Jeddah outbreak.
The samples were submitted to Jeddah regional laboratory on [3, 5 and 7 Apr 2014], and sent to Germany for external confirmatory testing on [14 Apr 2014] by KSA MOH in Riyadh.
Two of the sequenced viruses were from patients treated in the major public hospital in which most cases of the Jeddah outbreak seem to have occurred.
A 3rd sequence was from another health care facility in the city.
Genome sequences of all 3 viruses are highly similar to each other but not identical, and are highly similar to a large number of known MERS-CoV sequences (consult http://www.virology-bonn.de for a phylogeny; genome overview in Cotten 2014).
There are no genome insertions or deletions suggestive of sudden major changes.
The receptor-binding domain in the spike protein thought to influence the virus's ability to be transmitted or spread is 100 percent identical to the binding site in a large number of known MERS-CoV genome sequences.
Based on genome comparison with other MERS-CoV strains there is no reason to assume that the sequenced viruses from Jeddah have acquired changes increasing their pandemic potential.
As long as the sequences are in the draft stage, we are making them available on our homepage (http://www.virology-bonn.de ) and provide them to the epidemic blog (http://epidemic.bio.ed.ac.uk ).
They will be submitted to GenBank after some curating.
We have sequenced partial spike protein genes from another 25 viruses, showing 100 percent sequence identity with above-mentioned genomes.
However, more sequence information needs to be collected before inferences of transmission patterns can be reached (e.g., new acquisitions of infection, for example from animals or unlinked human communities, versus contingent [? contiguous] hospital-based transmission chains).
Of note, hospital-based transmission of MERS-CoV without evidence of changes in the genome of the involved virus has occurred previously, and has been controlled upon enforcement of infection control measures (Assiri 2013, Cotten 2013).
The samples we tested were dispatched to Germany by KSA MOH, Riyadh, on [14 Apr 2014] in the form of RNA extracts with a request for external confirmatory testing in view of the increasing case count in Jeddah.
29 samples had been tested positive in Jeddah regional laboratory by 2 different RT-PCR assays (the upE and 1A RT-PCR assays developed by my laboratory).
28 of these were confirmed in my lab using an alternative target gene (nucleocapsid) not available in Jeddah regional laboratory, excluding contamination at least after the stage of RNA preparation.
According to personal communications with laboratory staff in Jeddah, internal confirmatory testing (i.e., the re-testing by 1A assay of samples tested positive by upE assay) always involves the generation of a new RNA extract from the original clinical sample. (If this practice is complied with, factual contamination risk at the level of the laboratory is very low.)
In light of some of the recent comments implicating delays in following up on the outbreak it is worth considering the timing and the workload associated with careful testing and internal confirmation done in Jeddah.
It is also worth mentioning that samples were already dispatched from KSA MOH Riyadh to Germany on [14 Apr 2014] -- just about a week after receipt of samples in Jeddah regional laboratory, testing, internal confirmatory testing, and transport to Riyadh.
After dispatch from Riyadh, samples were not successfully delivered through customs in Germany with an administrative process that took 3 days (17 Apr 2014).
The sequencing work in Bonn started only on [22 Apr 2014] for the simple reason that most of the laboratory staff (including myself) have been on Easter holidays. Sequencing of further samples taken at later time points in Jeddah is underway.
Christian Drosten (also on behalf of Victor Corman who did the sequencing)
References:
- Assiri et al., N Engl J Med. 2013 Aug 1;369(5):407-16. doi: 10.1056/NEJMoa1306742. [full article available at: http://iacld.ir/DL/elm/hospitaloutbreakofmiddleeastrespiratorysyndromecor onavirusmerscov.pdf ]
- Cotten et al., Lancet. 2013 Dec 14;382(9909):1993-2002. doi: 10.1016/S0140-6736(13)61887-5. [full article available at: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2813%2961887-5/fulltext ]
- Cotten et al., MBio. 2014 Feb 18;5(1). pii: e01062-13. doi: 10.1128/mBio.01062-13 [full article available at: http://mbio.asm.org/content/5/1/e01062-13.full.pdf+html ]
- Corman et al., Euro Surveill. 2012 Sep 27;17(39). pii: 20285. [article available at: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20285 ]
- Corman et al., Euro Surveill. 2012 Dec 6;17(49). pii: 20334. [article available at: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20334
--
Christian Drosten, Institute of Virology, University of Bonn Medical Centre, Sigmund Freud Str 25, 53105 Bonn, Germany drosten@virology-bonn.de
[ProMED would like to thank Prof. Drosten for sharing this important and valuable information. There have been many rumors circulating pushing the theory that the MERS-CoV circulating in Jeddah has "mutated" with an adaptation for significantly enhanced human-to-human transmission.
These preliminary findings provide scientific evidence that at present the virus has not significantly altered its receptor sites affecting the virus's transmissibility potential.
This sequence evidence rather supports the idea that non-viral factors (e.g., epidemiologic, behavioral, environmental, host, etc.) have led to the recent upsurge in cases.
We look forward to the results on more recent specimens (from the past week or so) to see if there have been significant changes.
We also look forward to results of case control studies on these outbreaks (in Jeddah, Riyadh and the UAE) to further identify the risk factors for transmission in these outbreaks. - Mod.MPP]
(?)
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