Middle East respiratory syndrome coronavirus infection causes: Difference between revisions

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{{MERS}}
{{MERS}}
{{CMG}}; {{AE}} {{JS}}
{{CMG}}; {{AE}} {{JS}}
{{Taxobox
| color        = violet
| name          = MERS-CoV
| image        = MERS-CoV electron micrograph1.jpg
| image_caption = MERS-CoV particles as seen by negative stain electron microscopy. Virions contain characteristic club-like projections emanating from the viral membrane.
| virus_group  = iv
| ordo          = ''[[Nidovirales]]''
| familia      = ''[[Coronaviridae]]''
| subfamilia    = ''[[Coronavirinae]]''
| genus        = ''[[Betacoronavirus]]''
| species      = '''''MERS-CoV'''''
}}


==Overview==
==Overview==
Ten years after the outbreak of SARS-CoV, the MERS-CoV is identified as the agent of a lethal pneumonia in patients who have recently been related to the Arabian Peninsula. The [[Middle east respiratory syndrome]] [[coronavirus]] ([[MERS-CoV]]), also termed '''EMC/2012''' (HCoV-EMC/2012), is positive-sense, single-stranded [[RNA]] novel [[species]] of the genus ''Betacoronavirus''.<ref name=deGroot>{{cite journal
MERS-CoV is caused by a lineage C betacoronavirus, an enveloped, spherical (120 nm in diameter), single-stranded, positive-strand RNA virus that belongs to the family''[[Coronaviridae]]''of the order''[[Nidovirales]]. ''The natural reservoir of MERS-CoV is unknown, but bats are thought to be the most likely natural reservoir. MERS-CoV is thought to have a zoonotic activity, whereby transmission occurs from animals to humans. Limited data is available to confirm or rule out human-to-human transmission.
|author=De Groot RJ |title=Middle East Respiratory Syndrome Coronavirus (MERS-CoV): Announcement of the Coronavirus Study Group |journal=Journal of Virology |date=15 May 2013
|doi=10.1128/JVI.01244-13 |pmid=23678167 |pmc=3700179 |volume=87 |issue=14 |pages=7790–2|author-separator= |author2=and others |displayauthors=1 }}</ref><ref name="Perlman2013">{{cite journal|last1=Perlman|first1=S.|title=The Middle East Respiratory Syndrome--How Worried Should We Be?|journal=mBio|volume=4|issue=4|year=2013|pages=e00531-13–e00531-13|issn=2150-7511|doi=10.1128/mBio.00531-13}}</ref> First called ''novel coronavirus 2012'' or simply ''novel coronavirus'', it was first reported in 2012 after [[genome]] sequencing of the [[virus]], isolated from [[sputum]] samples of patients, affected by a 2012 outbreak of a "new [[flu]]". Until May 2013, [[MERS-CoV]] was being described as a ''[[SARS]]-like virus'' or colloquially as "Saudi [[SARS]]. Since then it is known to be distinct, not only from [[SARS-CoV]], but also from other known [[endemic]] [[coronaviruses]], such as betacoronavirus HCoV-OC43 and HCoV-HKU1, as well as from the [[common cold virus|common cold coronavirus]].<ref name=sciencenews27feb2013>{{cite news |first=Tina Hesman |last=Saey|title=Scientists race to understand deadly new virus: SARS-like infection causes severe illness, but may not spread quickly |journal=[[Science News]] |volume=183 |number=6 |date=27 February 2013| url=http://www.sciencenews.org/view/generic/id/348643/description/Scientists_race_to_understand_deadly_new_virus|page=5}}</ref> As of May 2014, several [[MERS-CoV]] cases have been reported in different countries, including Saudi Arabia, Malaysia, Jordan, Qatar, Egypt, the United Arab Emirates, Tunisia, Kuwait, Oman, Algeria, Bangladesh, the United Kingdom and the United States.<ref>{{cite web|url=http://rt.com/usa/158852-mers-florida-health-virus/|title=Patient with deadly MERS virus waited hours in Florida ER|date=2014-05-14|accessdate=2014-05-14}}</ref>


==Virology==
==Causes==
The [[Middle East respiratory syndrome]] [[coronavirus]] ([[MERS-CoV]]) is an emerging type of [[coronavirus]], specifically a ''betacoronavirus'' of the lineage C. The [[MERS-CoV]] is a single stranded, positive sense [[virus]], whose [[genome]] contains 30.119 [[nucleotides]] and encodes for structural and nonstructural [[proteins]]. The structural [[proteins]] located at the [[3' end]] of the [[RNA]] chain are also seen in the [[genome]] of other [[coronaviruses]] and may include:<ref name="Perlman2013">{{cite journal|last1=Perlman|first1=S.|title=The Middle East Respiratory Syndrome--How Worried Should We Be?|journal=mBio|volume=4|issue=4|year=2013|pages=e00531-13–e00531-13|issn=2150-7511|doi=10.1128/mBio.00531-13}}</ref><ref name="van Boheemende Graaf2012">{{cite journal|last1=van Boheemen|first1=S.|last2=de Graaf|first2=M.|last3=Lauber|first3=C.|last4=Bestebroer|first4=T. M.|last5=Raj|first5=V. S.|last6=Zaki|first6=A. M.|last7=Osterhaus|first7=A. D. M. E.|last8=Haagmans|first8=B. L.|last9=Gorbalenya|first9=A. E.|last10=Snijder|first10=E. J.|last11=Fouchier|first11=R. A. M.|title=Genomic Characterization of a Newly Discovered Coronavirus Associated with Acute Respiratory Distress Syndrome in Humans|journal=mBio|volume=3|issue=6|year=2012|pages=e00473-12–e00473-12|issn=2150-7511|doi=10.1128/mBio.00473-12}}</ref>
MERS-CoV is caused by a lineage C betacoronavirus.
*[[Nucleocapsid]] [[protein]].
*[[Glycoprotein]] for [[cell]] entry.
*2 [[membrane proteins]] for [[viral]] structure and assembly.
Within the [[genome]] of these 4 [[proteins]] are located [[RNA]] sequences that encode for 5 accessory [[proteins]], exclusive of [[MERS-CoV]] and that have no homology with other host [[proteins]]. Some of these have the purpose to facilitate the [[viral]] assembly or in evading the [[immune system]].<ref name="NarayananHuang2008">{{cite journal|last1=Narayanan|first1=Krishna|last2=Huang|first2=Cheng|last3=Makino|first3=Shinji|title=SARS coronavirus accessory proteins|journal=Virus Research|volume=133|issue=1|year=2008|pages=113–121|issn=01681702|doi=10.1016/j.virusres.2007.10.009}}</ref><ref name="van Boheemende Graaf2012">{{cite journal|last1=van Boheemen|first1=S.|last2=de Graaf|first2=M.|last3=Lauber|first3=C.|last4=Bestebroer|first4=T. M.|last5=Raj|first5=V. S.|last6=Zaki|first6=A. M.|last7=Osterhaus|first7=A. D. M. E.|last8=Haagmans|first8=B. L.|last9=Gorbalenya|first9=A. E.|last10=Snijder|first10=E. J.|last11=Fouchier|first11=R. A. M.|title=Genomic Characterization of a Newly Discovered Coronavirus Associated with Acute Respiratory Distress Syndrome in Humans|journal=mBio|volume=3|issue=6|year=2012|pages=e00473-12–e00473-12|issn=2150-7511|doi=10.1128/mBio.00473-12}}</ref>


===Origin===
===Taxonomy===
The first reported case of a [[human]] [[infected]] by [[MERS-CoV]] was in September 2012, in Saudi Arabia. This patient developed a [[lethal]] [[infection]] marked by a severe [[pneumonia]] and [[renal failure]]. However, some reports claim that the infection might have occurred first in a family from Jordan in April 2012. The [[virus]] was first isolated by an egyptian physician, while he was examining the [[lungs]] of a previously unknown [[MERS-CoV]] [[infected]] patient. The isolated [[infected]] [[cells]] showed [[cytopathic effect]] with [[syncytia]] formation and noted rounding.<ref name="rapid">{{cite web|url=http://www.ecdc.europa.eu/en/publications/Publications/novel-coronavirus-rapid-risk-assessment-update.pdf|title=ECDC Rapid Risk Assessment - Severe respiratory disease associated with a novel coronavirus|date=19 Feb 2013|accessdate=22 Apr 2014}}</ref><ref name=zaki8nov2012>{{cite journal |author=Ali Mohamed Zaki |author2=Sander van Boheemen |author3=Theo M. Bestebroer |author4=Albert D.M.E. Osterhaus |author5=Ron A.M. Fouchier |title=Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia |journal=New England Journal of Medicine |volume=367 |date=8 November 2012 |page=1814 |url=http://www.virology-bonn.de/fileadmin/user_upload/_temp_/Zaki_et_al.pdf |format=PDF |doi=10.1056/NEJMoa1211721|issue=19 }}</ref><ref name="thechart.blogs">{{cite news |last=Falco |first=Miriam |title=New SARS-like virus poses medical mystery |url= http://thechart.blogs.cnn.com/2012/09/24/new-sars-like-virus-poses-medical-mystery/ |accessdate=27 September 2012 |publisher=CNN |date=24 September 2012}}</ref><ref name="Zakivan Boheemen2012">{{cite journal|last1=Zaki|first1=Ali M.|last2=van Boheemen|first2=Sander|last3=Bestebroer|first3=Theo M.|last4=Osterhaus|first4=Albert D.M.E.|last5=Fouchier|first5=Ron A.M.|title=Isolation of a Novel Coronavirus from a Man with Pneumonia in Saudi Arabia|journal=New England Journal of Medicine|volume=367|issue=19|year=2012|pages=1814–1820|issn=0028-4793|doi=10.1056/NEJMoa1211721}}</ref>
 
In September 2012, a second case was reported in a 49 year old man in Qatar. This patient presented with [[Influenza history and symptoms#History and Symptoms|flu-like symptoms]] and the [[viral]] sequence was proved to be similar to the one from the first case. In November of the same year, identical cases kept appearing in Saudi Arabia and Qatar, with associated deaths.


Up until now it hasn't been determined if the [[infections]] were the result of a [[zoonotic]] event, with further human-to-human [[transmission]] or if they were a case of multiple [[zoonotic]] events from a common source. A study from the Riyadh University has suggested that, since the the [[virus]] first appeared, there may have been 7 different [[zoonotic]] [[transmissions]]. Although there are still limited data, it has been noted that the [[coronavirus]] has a large [[genetic]] diversity among [[animal]] reservoirs, yet the sample analysis of the [[infected]] patients suggests a common [[genome]] and therefore source. Since this early period, several clusters of [[infection]] have been created, suggesting that a human-to-human [[transmission]] has occurred.<ref name="Perlman2013">{{cite journal|last1=Perlman|first1=S.|title=The Middle East Respiratory Syndrome--How Worried Should We Be?|journal=mBio|volume=4|issue=4|year=2013|pages=e00531-13–e00531-13|issn=2150-7511|doi=10.1128/mBio.00531-13}}</ref>
Betacoronavirus is an enveloped, spherical (120 nm in diameter), single-stranded, positive-strand RNA virus that belongs to the family ''[[Coronaviridae]]'' of the order ''[[Nidovirales]].''


[[Molecular clock analysis]] studies have determined that the [[viruses]] from the EMC/2012 and from England/Qatar/2012 date from 2011. This suggests, not only a single [[zoonotic]] event as source of the reported cases, possibly implying that the [[MERS-CoV]] has been present [[Asymptomatic|asymptomatically]] in the [[human]] population for longer than one year without being detected, but also that it might have suffered an independent [[transmission]] from an unidentified source.<ref>{{cite web|url=http://wwwnc.cdc.gov/eid/article/19/5/13-0057_article.htm |title=Full-Genome Deep Sequencing and Phylogenetic Analysis of Novel Human Betacoronavirus - Vol. 19 No. 5 - May 2013 - CDC |publisher=[[Emerging Infectious Diseases]]|date=2013-05-19 |accessdate=2013-06-01}}</ref><ref>Lau SK, Lee P, Tsang AK, Yip CC, Tse H, Lee RA, Molecular epidemiology of human coronavirus OC43 reveals evolution of different genotypes over time and recent emergence of a novel genotype due to natural recombination. [[J Virol.]] 2011;85:11325–37. DOIExtract</ref>
===Genome===
The betacoronavirus contains a [[genome]] composed of 30,119 [[nucleotides]] that encodes structural and non-structural [[proteins]]. The genome is considered the largest among all RNA virus genomes, reaching 27-32 kb in size.


===Tropism===
===Tropism===
Studies have shown that in [[humans]], unlike most [[viruses]] that tend to [[infect]] [[ciliated]] [[cells]], [[MERS-CoV]] has a strong [[tropism]] for the [[cilium|nonciliated]] [[bronchial]] [[epithelium]]. Also, it has been noted that the [[virus]] has the capacity to evade the [[innate immune system]] and inhibit [[interferon]] production.<ref name="Kindler-2013">
* [[MERS-CoV]] has a strong [[tropism]] for the [[cilium|non-ciliated]] [[bronchial]] [[epithelium]].
{{Cite journal|last1=Kindler|first1=E.|last2=Jónsdóttir|first2=H. R.|last3=Muth|first3=D.|last4=Hamming|first4=O. J.|last5=Hartmann|first5=R.|last6=Rodriguez|first6=R.|last7=Geffers|first7=R.|last8=Fouchier|first8=R. A.|last9=Drosten|first9=C.|title=Efficient Replication of the Novel Human Betacoronavirus EMC on Primary Human Epithelium Highlights Its Zoonotic Potential|journal=MBio|volume=4|issue=1|pages=e00611–12|year=2013|doi= 10.1128/mBio.00611-12|pmid=23422412|pmc=3573664|display-authors=9}}</ref><ref name="Raj-2013">{{Cite journal|last1=Raj|first1=V. S.|last2=Mou|first2=H.|last3=Smits|first3=S. L.|last4=Dekkers|first4=D. H.|last5=Müller|first5=M. A.|last6=Dijkman|first6=R.|last7=Muth|first7=D.|last8=Demmers|first8=J. A.|last9=Zaki|first9 = A.|title=Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC|journal=Nature|volume=495|issue=7440|pages=251–4|date=March 2013|doi=10.1038/nature12005|pmid=23486063|display-authors=9}}</ref>
* Less commonly, MERS-CoV may primarily infect cells of the GI tract or the neurological system.  


It took only 6 months for the [[MERS-CoV]] [[receptor]] to be identified and published. Initially, due to the similarityies between the [[MERS-CoV]] and the [[SARS-CoV]], it was proposed that the [[MERS-CoV]] would use the same [[cell receptor|cellular receptor]] for [[infection]], as the [[SARS-CoV]], namely the [[Angiotensin-converting enzyme 2|angiotensin converting enzyme 2]].<ref name="Perlman2013">{{cite journal|last1=Perlman|first1=S.|title=The Middle East Respiratory Syndrome--How Worried Should We Be?|journal=mBio|volume=4|issue=4|year=2013|pages=e00531-13–e00531-13|issn=2150-7511|doi=10.1128/mBio.00531-13}}</ref><ref name="RajMou2013">{{cite journal|last1=Raj|first1=V. Stalin|last2=Mou|first2=Huihui|last3=Smits|first3=Saskia L.|last4=Dekkers|first4=Dick H. W.|last5=Müller|first5=Marcel A.|last6=Dijkman|first6=Ronald|last7=Muth|first7=Doreen|last8=Demmers|first8=Jeroen A. A.|last9=Zaki|first9=Ali|last10=Fouchier|first10=Ron A. M.|last11=Thiel|first11=Volker|last12=Drosten|first12=Christian|last13=Rottier|first13=Peter J. M.|last14=Osterhaus|first14=Albert D. M. E.|last15=Bosch|first15=Berend Jan|last16=Haagmans|first16=Bart L.|title=Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC|journal=Nature|volume=495|issue=7440|year=2013|pages=251–254|issn=0028-0836|doi=10.1038/nature12005}}</ref><ref name="MullerRaj2012">{{cite journal|last1=Muller|first1=M. A.|last2=Raj|first2=V. S.|last3=Muth|first3=D.|last4=Meyer|first4=B.|last5=Kallies|first5=S.|last6=Smits|first6=S. L.|last7=Wollny|first7=R.|last8=Bestebroer|first8=T. M.|last9=Specht|first9=S.|last10=Suliman|first10=T.|last11=Zimmermann|first11=K.|last12=Binger|first12=T.|last13=Eckerle|first13=I.|last14=Tschapka|first14=M.|last15=Zaki|first15=A. M.|last16=Osterhaus|first16=A. D. M. E.|last17=Fouchier|first17=R. A. M.|last18=Haagmans|first18=B. L.|last19=Drosten|first19=C.|title=Human Coronavirus EMC Does Not Require the SARS-Coronavirus Receptor and Maintains Broad Replicative Capability in Mammalian Cell Lines|journal=mBio|volume=3|issue=6|year=2012|pages=e00515-12–e00515-12|issn=2150-7511|doi=10.1128/mBio.00515-12}}</ref>
===Transmission===
However, the [[cell receptor|cellular receptor]] for [[MERS-CoV]] was later identified as being the ''dipeptidyl [[peptidase]] 4'' (DDP4) or ''CD26''.<ref name="Raj-2013" /> The ''DPP4 receptor'' is an ectopeptidase, which is similar to other [[molecules]] that other [[coronaviruses]] use to [[infect]] [[cells]], such as the ''human angiotensin-converting enzyme 2'', for [[SARS-CoV]], and the ''aminopeptidade N'', for alphacoronaviruses. The [[amino acid]] sequence of this [[receptor]] is a highly conserved sequence across [[species]], being expressed in human [[bronchial]] [[epithelium]] and [[kidneys]], and its [[enzymatic]] activity is not required for the process of [[infection]].<ref name="Raj-2013" /><ref name="dpp4_receptor">{{cite web|title=Receptor for new coronavirus found|url=http://www.nature.com/news/receptor-for-new-coronavirus-found-1.12584|date=2013-03-13|accessdate=2013-03-18|publisher=nature.com}}</ref> When comparing the [[receptor]] for [[MERS-CoV]] with the one for [[SARS-CoV]], it is important to notice that both are shed of the [[cell membrane|cell surface]] after the respective [[infections]]. In the case of [[SARS-CoV]], the loss of this [[receptor]] leads to the worsening of the condition, evolving to a more severe [[pulmonary disease]]. On the other hand, DDP4 is a [[neutrophil]] [[chemorepellent]] and its loss from the [[cell membrane|cell surface]] leads to [[cellular]] changes that may alter the composition of the [[immune cell]] infiltrate, which may consequently alter the evolution of the [[infectious]] state.<ref name="Perlman2013">{{cite journal|last1=Perlman|first1=S.|title=The Middle East Respiratory Syndrome--How Worried Should We Be?|journal=mBio|volume=4|issue=4|year=2013|pages=e00531-13–e00531-13|issn=2150-7511|doi=10.1128/mBio.00531-13}}</ref><ref name="pmid20134095">{{cite journal| author=Imai Y, Kuba K, Ohto-Nakanishi T, Penninger JM| title=Angiotensin-converting enzyme 2 (ACE2) in disease pathogenesis. | journal=Circ J | year= 2010 | volume= 74 | issue= 3 | pages= 405-10 | pmid=20134095 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20134095  }} </ref><ref name="pmid12892317">{{cite journal| author=Lambeir AM, Durinx C, Scharpé S, De Meester I| title=Dipeptidyl-peptidase IV from bench to bedside: an update on structural properties, functions, and clinical aspects of the enzyme DPP IV. | journal=Crit Rev Clin Lab Sci | year= 2003 | volume= 40 | issue= 3 | pages= 209-94 | pmid=12892317 | doi=10.1080/713609354 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12892317  }} </ref><ref name="pmid23677473">{{cite journal| author=Herlihy SE, Pilling D, Maharjan AS, Gomer RH| title=Dipeptidyl peptidase IV is a human and murine neutrophil chemorepellent. | journal=J Immunol | year= 2013 | volume= 190 | issue= 12 | pages= 6468-77 | pmid=23677473 | doi=10.4049/jimmunol.1202583 | pmc=PMC3756559 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23677473  }} </ref> After the binding of [[MERS-CoV]] to its [[cellular]] [[receptor]], a serious of actions, similar to ones from other [[coronaviruses]] and involving host [[proteases]], such as [[cathepsin B]], are triggered. These include the excision of the surface [[glycoprotein]], which will ultimately:<ref name="Perlman2013">{{cite journal|last1=Perlman|first1=S.|title=The Middle East Respiratory Syndrome--How Worried Should We Be?|journal=mBio|volume=4|issue=4|year=2013|pages=e00531-13–e00531-13|issn=2150-7511|doi=10.1128/mBio.00531-13}}</ref><ref name="GiererBertram2013">{{cite journal|last1=Gierer|first1=S.|last2=Bertram|first2=S.|last3=Kaup|first3=F.|last4=Wrensch|first4=F.|last5=Heurich|first5=A.|last6=Kramer-Kuhl|first6=A.|last7=Welsch|first7=K.|last8=Winkler|first8=M.|last9=Meyer|first9=B.|last10=Drosten|first10=C.|last11=Dittmer|first11=U.|last12=von Hahn|first12=T.|last13=Simmons|first13=G.|last14=Hofmann|first14=H.|last15=Pohlmann|first15=S.|title=The Spike Protein of the Emerging Betacoronavirus EMC Uses a Novel Coronavirus Receptor for Entry, Can Be Activated by TMPRSS2, and Is Targeted by Neutralizing Antibodies|journal=Journal of Virology|volume=87|issue=10|year=2013|pages=5502–5511|issn=0022-538X|doi=10.1128/JVI.00128-13}}</ref>
* MERS-CoV is thought to have a zoonotic activity, whereby transmission occurs from animals to humans.
*Expose fusion [[peptide]].
* Although bats are the natural host of the betacoronavirus, it is unknown if MERS coronavirus transmission to humans is through bats, through an intermediate animal hosts following crossover and subsequent adaptation, or through a completely different host.
*Allow fusion between [[virus]] and [[cell membrane]].
* Limited data is available to confirm or rule out human-to-human transmission.
*Lead to the release of the [[viral]] [[nucleocapsid]] into [[cellular]] [[cytoplasm]].


===Transmission===
===Natural Reservoir===
Since may 29th 2013, the [[WHO]] has warned that the [[MERS-CoV]] should be considered a "threat to the entire world".<ref name="Perlman2013">{{cite journal|last1=Perlman|first1=S.|title=The Middle East Respiratory Syndrome--How Worried Should We Be?|journal=mBio|volume=4|issue=4|year=2013|pages=e00531-13–e00531-13|issn=2150-7511|doi=10.1128/mBio.00531-13}}</ref> [[Transmission]] of [[MERS-CoV]] is prone to occur in [[immunocompromised]] patients, or in patients with other [[comorbidities]], such as [[diabetes]] or [[renal failure]].<ref name="Perlman2013">{{cite journal|last1=Perlman|first1=S.|title=The Middle East Respiratory Syndrome--How Worried Should We Be?|journal=mBio|volume=4|issue=4|year=2013|pages=e00531-13–e00531-13|issn=2150-7511|doi=10.1128/mBio.00531-13}}</ref> In a study of 23 patients of the largest [[outbreak]] so far, in Saudi Arabia, was determined that 74% had underlying [[diabetes mellitus]], 52% [[renal disease]] and 43% [[lung disease]], highlighting the impact of underlying [[comorbidities]] in the overall risk of [[infection]] with [[MERS-CoV]]. This evidence is further supported by the fact that cases of [[infected]] family members and health-care workers was only reported in 1 to 2% of contacts.<ref name="Perlman2013">{{cite journal|last1=Perlman|first1=S.|title=The Middle East Respiratory Syndrome--How Worried Should We Be?|journal=mBio|volume=4|issue=4|year=2013|pages=e00531-13–e00531-13|issn=2150-7511|doi=10.1128/mBio.00531-13}}</ref><ref name="AssiriMcGeer2013">{{cite journal|last1=Assiri|first1=Abdullah|last2=McGeer|first2=Allison|last3=Perl|first3=Trish M.|last4=Price|first4=Connie S.|last5=Al Rabeeah|first5=Abdullah A.|last6=Cummings|first6=Derek A.T.|last7=Alabdullatif|first7=Zaki N.|last8=Assad|first8=Maher|last9=Almulhim|first9=Abdulmohsen|last10=Makhdoom|first10=Hatem|last11=Madani|first11=Hossam|last12=Alhakeem|first12=Rafat|last13=Al-Tawfiq|first13=Jaffar A.|last14=Cotten|first14=Matthew|last15=Watson|first15=Simon J.|last16=Kellam|first16=Paul|last17=Zumla|first17=Alimuddin I.|last18=Memish|first18=Ziad A.|title=Hospital Outbreak of Middle East Respiratory Syndrome Coronavirus|journal=New England Journal of Medicine|volume=369|issue=5|year=2013|pages=407–416|issn=0028-4793|doi=10.1056/NEJMoa1306742}}</ref>
* The natural reservoir of MERS-CoV is unknown.
* The following are thought to be the natural reservoirs of MERS-CoV:
** Bats (The majority of reports hypothesized that bats are the natural reservoir of MERS-CoV)
** Camels
** Goats


At the present time it is not known the stage at which an [[infected]] [[MERS-CoV]] patient becomes [[contagious]], if he is able to [[transmission|transmit]] the [[virus]] while there is still no evidence [[respiratory illness]], or if there is [[transmission]] only after [[symptom]] onset. If the first is correct, then the the control of a larger [[outbreak]] will be more challenging, considering the prevalence of global traveling nowadays.<ref name="Perlman2013">{{cite journal|last1=Perlman|first1=S.|title=The Middle East Respiratory Syndrome--How Worried Should We Be?|journal=mBio|volume=4|issue=4|year=2013|pages=e00531-13–e00531-13|issn=2150-7511|doi=10.1128/mBio.00531-13}}</ref>
==Gallery==


One of the major gaps of knowledge about this [[virus]] is that its prevalence in the community is not known, therefore, and since most of the identified cases were patients with underlying [[comorbidities]], there is a possibility of [[MERS-CoV]] to be a common [[infection]] in Saudi-Arabia, with which patients without these comorbidties only develop minor [[respiratory]] [[symptoms]] or are [[asymptomatic]].<ref name="Perlman2013">{{cite journal|last1=Perlman|first1=S.|title=The Middle East Respiratory Syndrome--How Worried Should We Be?|journal=mBio|volume=4|issue=4|year=2013|pages=e00531-13–e00531-13|issn=2150-7511|doi=10.1128/mBio.00531-13}}</ref>
<gallery>


===Natural reservoir===
Image: Coronavirus14.jpeg| TEM reveals ultrastructural morphology of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
In contrast to the [[SARS-CoV]], that in its [[outbreak]] back in 2002/2003 had adapted so much to the [[human]] population that it could no longer [[infect]] bat [[cells]], the [[MERS-CoV]] is able to [[infect]] both [[animal]] and [[human]] [[cells]]. This fact suggests the existence of a possible bat to [[human]] [[transmission]].<ref name="MullerRaj2012">{{cite journal|last1=Muller|first1=M. A.|last2=Raj|first2=V. S.|last3=Muth|first3=D.|last4=Meyer|first4=B.|last5=Kallies|first5=S.|last6=Smits|first6=S. L.|last7=Wollny|first7=R.|last8=Bestebroer|first8=T. M.|last9=Specht|first9=S.|last10=Suliman|first10=T.|last11=Zimmermann|first11=K.|last12=Binger|first12=T.|last13=Eckerle|first13=I.|last14=Tschapka|first14=M.|last15=Zaki|first15=A. M.|last16=Osterhaus|first16=A. D. M. E.|last17=Fouchier|first17=R. A. M.|last18=Haagmans|first18=B. L.|last19=Drosten|first19=C.|title=Human Coronavirus EMC Does Not Require the SARS-Coronavirus Receptor and Maintains Broad Replicative Capability in Mammalian Cell Lines|journal=mBio|volume=3|issue=6|year=2012|pages=e00515-12–e00515-12|issn=2150-7511|doi=10.1128/mBio.00515-12}}</ref> However, considering the low probability of every [[infected]] [[human]] having been in contact with bats, it is more likely that another [[animal]] host, common in the Arabian Peninsula such as goats or camels, was the source for the [[infection]]. This is supported by the discovery of neutralizing [[antibodies]] for [[MERS-CoV]] in all dromedary camels of Oman, as well as by the full-[[genome]] sequence of [[MERS-CoV]] from dromedaries that was revealed to be 99.9% similar with the [[genome]] of [[human]] [[clade]] B of [[MERS-CoV]]. A further study on dromedary camels from Saudi Arabia, published in December 2013, revealed the presence of [[MERS-CoV]] in 90% of the evaluated dromedary camels, suggesting that dromedary camels not only could be the main reservoir of [[MERS-CoV]], but also the animal origin of [[MERS]]. This discoveries are of extreme relevance since they allow the definition of the [[human]] populations at risk, so that further protective measures might be taken.<ref name="ReuskenHaagmans2013">{{cite journal|last1=Reusken|first1=Chantal BEM|last2=Haagmans|first2=Bart L|last3=Müller|first3=Marcel A|last4=Gutierrez|first4=Carlos|last5=Godeke|first5=Gert-Jan|last6=Meyer|first6=Benjamin|last7=Muth|first7=Doreen|last8=Raj|first8=V Stalin|last9=Vries|first9=Laura Smits-De|last10=Corman|first10=Victor M|last11=Drexler|first11=Jan-Felix|last12=Smits|first12=Saskia L|last13=El Tahir|first13=Yasmin E|last14=De Sousa|first14=Rita|last15=van Beek|first15=Janko|last16=Nowotny|first16=Norbert|last17=van Maanen|first17=Kees|last18=Hidalgo-Hermoso|first18=Ezequiel|last19=Bosch|first19=Berend-Jan|last20=Rottier|first20=Peter|last21=Osterhaus|first21=Albert|last22=Gortázar-Schmidt|first22=Christian|last23=Drosten|first23=Christian|last24=Koopmans|first24=Marion PG|title=Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study|journal=The Lancet Infectious Diseases|volume=13|issue=10|year=2013|pages=859–866|issn=14733099|doi=10.1016/S1473-3099(13)70164-6}}</ref><ref>{{cite web|url=http://dx.doi.org/10.3201/eid2007.140571|title=MERS coronavirus in dromedary camel herd, Saudi Arabia.|last=Hemida first=Maged G|last2=Chu|first2=Daniel KW|last3=Poon|first3=Ranawaka|last4=Perera|first4=Mohammad A A|last5=Ng|first5= Hoiyee-Y|quote=The full-genome sequence of MERS-CoV from dromedaries in this study is 99.9% similar to genomes of human clade B MERS-CoV.|date=Jul 2014|accessdate=22 Apr 2014}}</ref><ref>{{cite journal|last=Hemida|first=MG|title=Middle East Respiratory Syndrome (MERS) coronavirus seroprevalence in domestic livestock in Saudi Arabia, 2010 to 2013|journal=Euro Surveillance|date=2013|volume=18|issue=50|url=http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20659}}</ref>
Image: Coronavirus13.jpeg| TEM reveals ultrastructural morphology of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
According to the March 2014 [[MERS-CoV]] summary update from the [[WHO]], recent studies claim that camels serve as the primary source of the [[MERS-CoV]] [[infection]] in [[humans]], while bats may be the ultimate reservoir of the [[virus]]. Evidence includes the frequency with which the [[virus]] has been found in camels, to which [[human]] cases have been exposed, seriological data which shows widespread [[transmission]] in camels and the similarity of the camel [[coronavirus]] to the [[human]] type.<ref>{{cite web|url=http://www.who.int/csr/disease/coronavirus_infections/MERS_CoV_Update_27_March_2014.pdf?ua=1|title=Middle East respiratory syndrome coronavirus (MERS‐CoV)Summary and literature update – as of 27 March2014|date=27 Mar 2014|accessdate=24 Apr 2014}}</ref>
Image: Coronavirus12.jpeg| TEM reveals ultrastructural morphology of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Coronavirus11.jpeg| Middle East Respiratory Syndrome Coronavirus (MERS-CoV) viral particles. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Coronavirus09.jpeg| Middle East Respiratory Syndrome Coronavirus (MERS-CoV) virion. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Coronavirus08.jpeg|TEM reveals ultrastructural details exhibited by three spherical-shaped Middle East Respiratory Syndrome Coronavirus (MERS-CoV) virions. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Coronavirus07.jpeg|TEM reveals ultrastructural details exhibited by a number of spherical-shaped Middle East Respiratory Syndrome Coronavirus (MERS-CoV) virions. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>


===Taxonomy===
Image: Coronavirus06.jpeg|TEM reveals ultrastructural details exhibited by a number of red-colored, spherical-shaped Middle East Respiratory Syndrome Coronavirus (MERS-CoV) virions. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Lineage: [[Viruses]]; ssRNA [[viruses]]; ss[[RNA]] positive-strand [[viruses]], no [[DNA]] stage; ''[[Nidovirales]]''; ''[[Coronaviridae]]''; ''Coronavirinae''; ''Betacoronavirus''; unclassified ''Betacoronavirus''
Image: Coronavirus05.jpeg|TEM reveals ultrastructural details exhibited by five spherical-shaped Middle East Respiratory Syndrome Coronavirus (MERS-CoV) virions, which were colorized yellow. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Coronavirus04.jpeg|TEM reveals ultrastructural details exhibited by a single, spherical-shaped Middle East Respiratory Syndrome Coronavirus (MERS-CoV) virion. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Coronavirus03.jpeg|TEM reveals ultrastructural details exhibited by a single, spherical-shaped Middle East Respiratory Syndrome Coronavirus (MERS-CoV) virion. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Coronavirus02.jpeg|SEM reveals ultrastructural details at the site of interaction of two spherical-shaped Middle East Respiratory Syndrome Coronavirus (MERS-CoV) viral particles, colorized blue, that were on the surface of a camel epithelial cell, colorized red. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Coronavirus01.jpeg|SEM reveals ultrastructural details at the site of interaction of numerous yellow-colored Middle East respiratory syndrome Coronavirus (MERS-CoV) viral particles on the surface of a Vero E6 cell (blue). <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>


==Microbiology==
{| style="float: right;"
| [[File:MERS electron micrograph.jpg|250px|thumb|none|This negatively-stained transmission electron micrograph revealed ultrastructural morphology of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). <SMALL>Courtesy: ''[http://phil.cdc.gov/phil/home.asp Public Health Image Library (PHIL), Centers for Disease Control and Prevention (CDC)]''<ref>{{Cite web | title = http://phil.cdc.gov/phil/details.asp | url = http://phil.cdc.gov/phil/details.asp}}</ref></SMALL>]]
|-
| [[File:MERS electron micrograph 3.jpg|250px|thumb|none|This highly-magnified negatively-stained transmission electron micrograph revealed ultrastructural morphology of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). <SMALL>Courtesy: ''[http://phil.cdc.gov/phil/home.asp Public Health Image Library (PHIL), Centers for Disease Control and Prevention (CDC)]''<ref>{{Cite web | title = http://phil.cdc.gov/phil/details.asp | url = http://phil.cdc.gov/phil/details.asp}}</ref></SMALL>]]
|-
| [[File:MERS electron micrograph 2.jpg|250px|thumb|none|This thin section transmission electron micrograph revealed ultrastructural morphology of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). <SMALL>Courtesy: ''[http://phil.cdc.gov/phil/home.asp Public Health Image Library (PHIL), Centers for Disease Control and Prevention (CDC)]''<ref>{{Cite web | title = http://phil.cdc.gov/phil/details.asp | url = http://phil.cdc.gov/phil/details.asp}}</ref></SMALL>]]
|-
| [[File:MERS electron micrograph 4.jpg|250px|thumb|none|This highly-magnified transmission electron micrograph revealed the presence of numerous Middle East Respiratory Syndrome Coronavirus (MERS-CoV) virions in this tissue culture sample. <SMALL>Courtesy: ''[http://phil.cdc.gov/phil/home.asp Public Health Image Library (PHIL), Centers for Disease Control and Prevention (CDC)]''<ref>{{Cite web | title = http://phil.cdc.gov/phil/details.asp | url = http://phil.cdc.gov/phil/details.asp}}</ref></SMALL>]]
|-
| [[File:MERS electron micrograph 5.jpg|250px|thumb|none|This highly-magnified transmission electron micrograph revealed the presence of numerous Middle East Respiratory Syndrome Coronavirus (MERS-CoV) virions in this tissue culture sample. <SMALL>Courtesy: ''[http://phil.cdc.gov/phil/home.asp Public Health Image Library (PHIL), Centers for Disease Control and Prevention (CDC)]''<ref>{{Cite web | title = http://phil.cdc.gov/phil/details.asp | url = http://phil.cdc.gov/phil/details.asp}}</ref></SMALL>]]
|}


The virus grows readily on [[Vero cells]] and LLC-MK2 cells.<ref name="promedmail.org"/>
</gallery>


==Corona Map==
==Related chapters==
There are a number of mapping efforts focused on tracking MERS coronavirus. On 2 May 2014, the [http://CoronaMap.com/ Corona Map] was launched to track the MERS coronavirus in realtime on the world map. The data is officially reported by WHO or the [[Ministry of Health]] of the respective country.<ref name=CoronaMap>{{cite press release|title=Corona Map|date=2 May 2014|url=http://CoronaMap.com}}</ref> [[HealthMap]] also tracks case reports with inclusion of news and social media as data sources as part of [http://healthmap.org/MERS HealthMap MERS].
* [[Middle East respiratory syndrome coronavirus]]


==References==
==References==
{{Reflist|2}}
{{Reflist|2}}


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[[category:Disease]]
[[category:Disease]]
[[Category:Infectious disease]]
 
[[category:Virology]]
[[category:Virology]]

Latest revision as of 18:04, 18 September 2017

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]

Overview

MERS-CoV is caused by a lineage C betacoronavirus, an enveloped, spherical (120 nm in diameter), single-stranded, positive-strand RNA virus that belongs to the familyCoronaviridaeof the orderNidovirales. The natural reservoir of MERS-CoV is unknown, but bats are thought to be the most likely natural reservoir. MERS-CoV is thought to have a zoonotic activity, whereby transmission occurs from animals to humans. Limited data is available to confirm or rule out human-to-human transmission.

Causes

MERS-CoV is caused by a lineage C betacoronavirus.

Taxonomy

Betacoronavirus is an enveloped, spherical (120 nm in diameter), single-stranded, positive-strand RNA virus that belongs to the family Coronaviridae of the order Nidovirales.

Genome

The betacoronavirus contains a genome composed of 30,119 nucleotides that encodes structural and non-structural proteins. The genome is considered the largest among all RNA virus genomes, reaching 27-32 kb in size.

Tropism

Transmission

  • MERS-CoV is thought to have a zoonotic activity, whereby transmission occurs from animals to humans.
  • Although bats are the natural host of the betacoronavirus, it is unknown if MERS coronavirus transmission to humans is through bats, through an intermediate animal hosts following crossover and subsequent adaptation, or through a completely different host.
  • Limited data is available to confirm or rule out human-to-human transmission.

Natural Reservoir

  • The natural reservoir of MERS-CoV is unknown.
  • The following are thought to be the natural reservoirs of MERS-CoV:
    • Bats (The majority of reports hypothesized that bats are the natural reservoir of MERS-CoV)
    • Camels
    • Goats

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References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 "Public Health Image Library (PHIL)".

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