Lack of Middle East Respiratory Syndrome Coronavirus Transmission in Rabbits
Identifieur interne : 001220 ( Pmc/Curation ); précédent : 001219; suivant : 001221Lack of Middle East Respiratory Syndrome Coronavirus Transmission in Rabbits
Auteurs : W. Widagdo ; Nisreen M. A. Okba ; Mathilde Richard ; Dennis De Meulder ; Theo M. Bestebroer ; Pascal Lexmond ; Elmoubasher A. B. A. Farag ; Mohammed Al-Hajri ; Koert J. Stittelaar ; Leon De Waal ; Geert Van Amerongen ; Judith M. A. Van Den Brand ; Bart L. Haagmans ; Sander HerfstSource :
- Viruses [ 1999-4915 ] ; 2019.
Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) transmission from dromedaries to humans has resulted in major outbreaks in the Middle East. Although some other livestock animal species have been shown to be susceptible to MERS-CoV, it is not fully understood why the spread of the virus in these animal species has not been observed in the field. In this study, we used rabbits to further characterize the transmission potential of MERS-CoV. In line with the presence of MERS-CoV receptor in the rabbit nasal epithelium, high levels of viral RNA were shed from the nose following virus inoculation. However, unlike MERS-CoV-infected dromedaries, these rabbits did not develop clinical manifestations including nasal discharge and did shed only limited amounts of infectious virus from the nose. Consistently, no transmission by contact or airborne routes was observed in rabbits. Our data indicate that despite relatively high viral RNA levels produced, low levels of infectious virus are excreted in the upper respiratory tract of rabbits as compared to dromedary camels, thus resulting in a lack of viral transmission.
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DOI: 10.3390/v11040381
PubMed: 31022948
PubMed Central: 6520746
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Lack of Middle East Respiratory Syndrome Coronavirus Transmission in Rabbits</title><author><name sortKey="Widagdo, W" sort="Widagdo, W" uniqKey="Widagdo W" first="W." last="Widagdo">W. Widagdo</name><affiliation><nlm:aff id="af1-viruses-11-00381">Department of Viroscience, Erasmus Medical Center, 3015GD Rotterdam, The Netherlands;<email>w.widagdo@erasmusmc.nl</email> (W.W.);<email>n.okba@erasmusmc.nl</email> (N.M.A.O.);<email>m.richard@erasmusmc.nl</email> (M.R.);<email>d.demeulder@erasmusmc.nl</email> (D.d.M.);<email>t.bestebroer@erasmusmc.nl</email> (T.M.B.);<email>p.lexmond@erasmusmc.nl</email> (P.L.);<email>j.m.a.vandenbrand@uu.nl</email> (J.M.A.v.d.B.);<email>s.herfst@erasmusmc.nl</email> (S.H.)</nlm:aff></affiliation></author><author><name sortKey="Okba, Nisreen M A" sort="Okba, Nisreen M A" uniqKey="Okba N" first="Nisreen M. A." last="Okba">Nisreen M. A. Okba</name><affiliation><nlm:aff id="af1-viruses-11-00381">Department of Viroscience, Erasmus Medical Center, 3015GD Rotterdam, The Netherlands;<email>w.widagdo@erasmusmc.nl</email> (W.W.);<email>n.okba@erasmusmc.nl</email> (N.M.A.O.);<email>m.richard@erasmusmc.nl</email> (M.R.);<email>d.demeulder@erasmusmc.nl</email> (D.d.M.);<email>t.bestebroer@erasmusmc.nl</email> (T.M.B.);<email>p.lexmond@erasmusmc.nl</email> (P.L.);<email>j.m.a.vandenbrand@uu.nl</email> (J.M.A.v.d.B.);<email>s.herfst@erasmusmc.nl</email> (S.H.)</nlm:aff></affiliation></author><author><name sortKey="Richard, Mathilde" sort="Richard, Mathilde" uniqKey="Richard M" first="Mathilde" last="Richard">Mathilde Richard</name><affiliation><nlm:aff id="af1-viruses-11-00381">Department of Viroscience, Erasmus Medical Center, 3015GD Rotterdam, The Netherlands;<email>w.widagdo@erasmusmc.nl</email> (W.W.);<email>n.okba@erasmusmc.nl</email> (N.M.A.O.);<email>m.richard@erasmusmc.nl</email> (M.R.);<email>d.demeulder@erasmusmc.nl</email> (D.d.M.);<email>t.bestebroer@erasmusmc.nl</email> (T.M.B.);<email>p.lexmond@erasmusmc.nl</email> (P.L.);<email>j.m.a.vandenbrand@uu.nl</email> (J.M.A.v.d.B.);<email>s.herfst@erasmusmc.nl</email> (S.H.)</nlm:aff></affiliation></author><author><name sortKey="De Meulder, Dennis" sort="De Meulder, Dennis" uniqKey="De Meulder D" first="Dennis" last="De Meulder">Dennis De Meulder</name><affiliation><nlm:aff id="af1-viruses-11-00381">Department of Viroscience, Erasmus Medical Center, 3015GD Rotterdam, The Netherlands;<email>w.widagdo@erasmusmc.nl</email> (W.W.);<email>n.okba@erasmusmc.nl</email> (N.M.A.O.);<email>m.richard@erasmusmc.nl</email> (M.R.);<email>d.demeulder@erasmusmc.nl</email> (D.d.M.);<email>t.bestebroer@erasmusmc.nl</email> (T.M.B.);<email>p.lexmond@erasmusmc.nl</email> (P.L.);<email>j.m.a.vandenbrand@uu.nl</email> (J.M.A.v.d.B.);<email>s.herfst@erasmusmc.nl</email> (S.H.)</nlm:aff></affiliation></author><author><name sortKey="Bestebroer, Theo M" sort="Bestebroer, Theo M" uniqKey="Bestebroer T" first="Theo M." last="Bestebroer">Theo M. Bestebroer</name><affiliation><nlm:aff id="af1-viruses-11-00381">Department of Viroscience, Erasmus Medical Center, 3015GD Rotterdam, The Netherlands;<email>w.widagdo@erasmusmc.nl</email> (W.W.);<email>n.okba@erasmusmc.nl</email> (N.M.A.O.);<email>m.richard@erasmusmc.nl</email> (M.R.);<email>d.demeulder@erasmusmc.nl</email> (D.d.M.);<email>t.bestebroer@erasmusmc.nl</email> (T.M.B.);<email>p.lexmond@erasmusmc.nl</email> (P.L.);<email>j.m.a.vandenbrand@uu.nl</email> (J.M.A.v.d.B.);<email>s.herfst@erasmusmc.nl</email> (S.H.)</nlm:aff></affiliation></author><author><name sortKey="Lexmond, Pascal" sort="Lexmond, Pascal" uniqKey="Lexmond P" first="Pascal" last="Lexmond">Pascal Lexmond</name><affiliation><nlm:aff id="af1-viruses-11-00381">Department of Viroscience, Erasmus Medical Center, 3015GD Rotterdam, The Netherlands;<email>w.widagdo@erasmusmc.nl</email> (W.W.);<email>n.okba@erasmusmc.nl</email> (N.M.A.O.);<email>m.richard@erasmusmc.nl</email> (M.R.);<email>d.demeulder@erasmusmc.nl</email> (D.d.M.);<email>t.bestebroer@erasmusmc.nl</email> (T.M.B.);<email>p.lexmond@erasmusmc.nl</email> (P.L.);<email>j.m.a.vandenbrand@uu.nl</email> (J.M.A.v.d.B.);<email>s.herfst@erasmusmc.nl</email> (S.H.)</nlm:aff></affiliation></author><author><name sortKey="Farag, Elmoubasher A B A" sort="Farag, Elmoubasher A B A" uniqKey="Farag E" first="Elmoubasher A. B. A." last="Farag">Elmoubasher A. B. A. Farag</name><affiliation><nlm:aff id="af2-viruses-11-00381">Ministry of Public Health, Doha, Qatar, PO Box. 42;<email>eabdfarag@MOPH.GOV.QA</email> (E.A.B.A.F.);<email>malhajri1@MOPH.GOV.QA</email> (M.A.-H.)</nlm:aff></affiliation></author><author><name sortKey="Al Hajri, Mohammed" sort="Al Hajri, Mohammed" uniqKey="Al Hajri M" first="Mohammed" last="Al-Hajri">Mohammed Al-Hajri</name><affiliation><nlm:aff id="af2-viruses-11-00381">Ministry of Public Health, Doha, Qatar, PO Box. 42;<email>eabdfarag@MOPH.GOV.QA</email> (E.A.B.A.F.);<email>malhajri1@MOPH.GOV.QA</email> (M.A.-H.)</nlm:aff></affiliation></author><author><name sortKey="Stittelaar, Koert J" sort="Stittelaar, Koert J" uniqKey="Stittelaar K" first="Koert J." last="Stittelaar">Koert J. Stittelaar</name><affiliation><nlm:aff id="af3-viruses-11-00381">Viroclinics Biosciences BV, Rotterdam 3029 AK, The Netherlands;<email>stittelaar@viroclinics.com</email> (K.J.S.);<email>dewaal@viroclinics.com</email> (L.d.W.);<email>amerongen@viroclinics.com</email> (G.v.A.)</nlm:aff></affiliation></author><author><name sortKey="De Waal, Leon" sort="De Waal, Leon" uniqKey="De Waal L" first="Leon" last="De Waal">Leon De Waal</name><affiliation><nlm:aff id="af3-viruses-11-00381">Viroclinics Biosciences BV, Rotterdam 3029 AK, The Netherlands;<email>stittelaar@viroclinics.com</email> (K.J.S.);<email>dewaal@viroclinics.com</email> (L.d.W.);<email>amerongen@viroclinics.com</email> (G.v.A.)</nlm:aff></affiliation></author><author><name sortKey="Van Amerongen, Geert" sort="Van Amerongen, Geert" uniqKey="Van Amerongen G" first="Geert" last="Van Amerongen">Geert Van Amerongen</name><affiliation><nlm:aff id="af3-viruses-11-00381">Viroclinics Biosciences BV, Rotterdam 3029 AK, The Netherlands;<email>stittelaar@viroclinics.com</email> (K.J.S.);<email>dewaal@viroclinics.com</email> (L.d.W.);<email>amerongen@viroclinics.com</email> (G.v.A.)</nlm:aff></affiliation></author><author><name sortKey="Van Den Brand, Judith M A" sort="Van Den Brand, Judith M A" uniqKey="Van Den Brand J" first="Judith M. A." last="Van Den Brand">Judith M. A. Van Den Brand</name><affiliation><nlm:aff id="af1-viruses-11-00381">Department of Viroscience, Erasmus Medical Center, 3015GD Rotterdam, The Netherlands;<email>w.widagdo@erasmusmc.nl</email> (W.W.);<email>n.okba@erasmusmc.nl</email> (N.M.A.O.);<email>m.richard@erasmusmc.nl</email> (M.R.);<email>d.demeulder@erasmusmc.nl</email> (D.d.M.);<email>t.bestebroer@erasmusmc.nl</email> (T.M.B.);<email>p.lexmond@erasmusmc.nl</email> (P.L.);<email>j.m.a.vandenbrand@uu.nl</email> (J.M.A.v.d.B.);<email>s.herfst@erasmusmc.nl</email> (S.H.)</nlm:aff></affiliation></author><author><name sortKey="Haagmans, Bart L" sort="Haagmans, Bart L" uniqKey="Haagmans B" first="Bart L." last="Haagmans">Bart L. Haagmans</name><affiliation><nlm:aff id="af1-viruses-11-00381">Department of Viroscience, Erasmus Medical Center, 3015GD Rotterdam, The Netherlands;<email>w.widagdo@erasmusmc.nl</email> (W.W.);<email>n.okba@erasmusmc.nl</email> (N.M.A.O.);<email>m.richard@erasmusmc.nl</email> (M.R.);<email>d.demeulder@erasmusmc.nl</email> (D.d.M.);<email>t.bestebroer@erasmusmc.nl</email> (T.M.B.);<email>p.lexmond@erasmusmc.nl</email> (P.L.);<email>j.m.a.vandenbrand@uu.nl</email> (J.M.A.v.d.B.);<email>s.herfst@erasmusmc.nl</email> (S.H.)</nlm:aff></affiliation></author><author><name sortKey="Herfst, Sander" sort="Herfst, Sander" uniqKey="Herfst S" first="Sander" last="Herfst">Sander Herfst</name><affiliation><nlm:aff id="af1-viruses-11-00381">Department of Viroscience, Erasmus Medical Center, 3015GD Rotterdam, The Netherlands;<email>w.widagdo@erasmusmc.nl</email> (W.W.);<email>n.okba@erasmusmc.nl</email> (N.M.A.O.);<email>m.richard@erasmusmc.nl</email> (M.R.);<email>d.demeulder@erasmusmc.nl</email> (D.d.M.);<email>t.bestebroer@erasmusmc.nl</email> (T.M.B.);<email>p.lexmond@erasmusmc.nl</email> (P.L.);<email>j.m.a.vandenbrand@uu.nl</email> (J.M.A.v.d.B.);<email>s.herfst@erasmusmc.nl</email> (S.H.)</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31022948</idno><idno type="pmc">6520746</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520746</idno><idno type="RBID">PMC:6520746</idno><idno type="doi">10.3390/v11040381</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">001220</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001220</idno><idno type="wicri:Area/Pmc/Curation">001220</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">001220</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Lack of Middle East Respiratory Syndrome Coronavirus Transmission in Rabbits</title><author><name sortKey="Widagdo, W" sort="Widagdo, W" uniqKey="Widagdo W" first="W." last="Widagdo">W. Widagdo</name><affiliation><nlm:aff id="af1-viruses-11-00381">Department of Viroscience, Erasmus Medical Center, 3015GD Rotterdam, The Netherlands;<email>w.widagdo@erasmusmc.nl</email> (W.W.);<email>n.okba@erasmusmc.nl</email> (N.M.A.O.);<email>m.richard@erasmusmc.nl</email> (M.R.);<email>d.demeulder@erasmusmc.nl</email> (D.d.M.);<email>t.bestebroer@erasmusmc.nl</email> (T.M.B.);<email>p.lexmond@erasmusmc.nl</email> (P.L.);<email>j.m.a.vandenbrand@uu.nl</email> (J.M.A.v.d.B.);<email>s.herfst@erasmusmc.nl</email> (S.H.)</nlm:aff></affiliation></author><author><name sortKey="Okba, Nisreen M A" sort="Okba, Nisreen M A" uniqKey="Okba N" first="Nisreen M. A." last="Okba">Nisreen M. A. Okba</name><affiliation><nlm:aff id="af1-viruses-11-00381">Department of Viroscience, Erasmus Medical Center, 3015GD Rotterdam, The Netherlands;<email>w.widagdo@erasmusmc.nl</email> (W.W.);<email>n.okba@erasmusmc.nl</email> (N.M.A.O.);<email>m.richard@erasmusmc.nl</email> (M.R.);<email>d.demeulder@erasmusmc.nl</email> (D.d.M.);<email>t.bestebroer@erasmusmc.nl</email> (T.M.B.);<email>p.lexmond@erasmusmc.nl</email> (P.L.);<email>j.m.a.vandenbrand@uu.nl</email> (J.M.A.v.d.B.);<email>s.herfst@erasmusmc.nl</email> (S.H.)</nlm:aff></affiliation></author><author><name sortKey="Richard, Mathilde" sort="Richard, Mathilde" uniqKey="Richard M" first="Mathilde" last="Richard">Mathilde Richard</name><affiliation><nlm:aff id="af1-viruses-11-00381">Department of Viroscience, Erasmus Medical Center, 3015GD Rotterdam, The Netherlands;<email>w.widagdo@erasmusmc.nl</email> (W.W.);<email>n.okba@erasmusmc.nl</email> (N.M.A.O.);<email>m.richard@erasmusmc.nl</email> (M.R.);<email>d.demeulder@erasmusmc.nl</email> (D.d.M.);<email>t.bestebroer@erasmusmc.nl</email> (T.M.B.);<email>p.lexmond@erasmusmc.nl</email> (P.L.);<email>j.m.a.vandenbrand@uu.nl</email> (J.M.A.v.d.B.);<email>s.herfst@erasmusmc.nl</email> (S.H.)</nlm:aff></affiliation></author><author><name sortKey="De Meulder, Dennis" sort="De Meulder, Dennis" uniqKey="De Meulder D" first="Dennis" last="De Meulder">Dennis De Meulder</name><affiliation><nlm:aff id="af1-viruses-11-00381">Department of Viroscience, Erasmus Medical Center, 3015GD Rotterdam, The Netherlands;<email>w.widagdo@erasmusmc.nl</email> (W.W.);<email>n.okba@erasmusmc.nl</email> (N.M.A.O.);<email>m.richard@erasmusmc.nl</email> (M.R.);<email>d.demeulder@erasmusmc.nl</email> (D.d.M.);<email>t.bestebroer@erasmusmc.nl</email> (T.M.B.);<email>p.lexmond@erasmusmc.nl</email> (P.L.);<email>j.m.a.vandenbrand@uu.nl</email> (J.M.A.v.d.B.);<email>s.herfst@erasmusmc.nl</email> (S.H.)</nlm:aff></affiliation></author><author><name sortKey="Bestebroer, Theo M" sort="Bestebroer, Theo M" uniqKey="Bestebroer T" first="Theo M." last="Bestebroer">Theo M. Bestebroer</name><affiliation><nlm:aff id="af1-viruses-11-00381">Department of Viroscience, Erasmus Medical Center, 3015GD Rotterdam, The Netherlands;<email>w.widagdo@erasmusmc.nl</email> (W.W.);<email>n.okba@erasmusmc.nl</email> (N.M.A.O.);<email>m.richard@erasmusmc.nl</email> (M.R.);<email>d.demeulder@erasmusmc.nl</email> (D.d.M.);<email>t.bestebroer@erasmusmc.nl</email> (T.M.B.);<email>p.lexmond@erasmusmc.nl</email> (P.L.);<email>j.m.a.vandenbrand@uu.nl</email> (J.M.A.v.d.B.);<email>s.herfst@erasmusmc.nl</email> (S.H.)</nlm:aff></affiliation></author><author><name sortKey="Lexmond, Pascal" sort="Lexmond, Pascal" uniqKey="Lexmond P" first="Pascal" last="Lexmond">Pascal Lexmond</name><affiliation><nlm:aff id="af1-viruses-11-00381">Department of Viroscience, Erasmus Medical Center, 3015GD Rotterdam, The Netherlands;<email>w.widagdo@erasmusmc.nl</email> (W.W.);<email>n.okba@erasmusmc.nl</email> (N.M.A.O.);<email>m.richard@erasmusmc.nl</email> (M.R.);<email>d.demeulder@erasmusmc.nl</email> (D.d.M.);<email>t.bestebroer@erasmusmc.nl</email> (T.M.B.);<email>p.lexmond@erasmusmc.nl</email> (P.L.);<email>j.m.a.vandenbrand@uu.nl</email> (J.M.A.v.d.B.);<email>s.herfst@erasmusmc.nl</email> (S.H.)</nlm:aff></affiliation></author><author><name sortKey="Farag, Elmoubasher A B A" sort="Farag, Elmoubasher A B A" uniqKey="Farag E" first="Elmoubasher A. B. A." last="Farag">Elmoubasher A. B. A. Farag</name><affiliation><nlm:aff id="af2-viruses-11-00381">Ministry of Public Health, Doha, Qatar, PO Box. 42;<email>eabdfarag@MOPH.GOV.QA</email> (E.A.B.A.F.);<email>malhajri1@MOPH.GOV.QA</email> (M.A.-H.)</nlm:aff></affiliation></author><author><name sortKey="Al Hajri, Mohammed" sort="Al Hajri, Mohammed" uniqKey="Al Hajri M" first="Mohammed" last="Al-Hajri">Mohammed Al-Hajri</name><affiliation><nlm:aff id="af2-viruses-11-00381">Ministry of Public Health, Doha, Qatar, PO Box. 42;<email>eabdfarag@MOPH.GOV.QA</email> (E.A.B.A.F.);<email>malhajri1@MOPH.GOV.QA</email> (M.A.-H.)</nlm:aff></affiliation></author><author><name sortKey="Stittelaar, Koert J" sort="Stittelaar, Koert J" uniqKey="Stittelaar K" first="Koert J." last="Stittelaar">Koert J. Stittelaar</name><affiliation><nlm:aff id="af3-viruses-11-00381">Viroclinics Biosciences BV, Rotterdam 3029 AK, The Netherlands;<email>stittelaar@viroclinics.com</email> (K.J.S.);<email>dewaal@viroclinics.com</email> (L.d.W.);<email>amerongen@viroclinics.com</email> (G.v.A.)</nlm:aff></affiliation></author><author><name sortKey="De Waal, Leon" sort="De Waal, Leon" uniqKey="De Waal L" first="Leon" last="De Waal">Leon De Waal</name><affiliation><nlm:aff id="af3-viruses-11-00381">Viroclinics Biosciences BV, Rotterdam 3029 AK, The Netherlands;<email>stittelaar@viroclinics.com</email> (K.J.S.);<email>dewaal@viroclinics.com</email> (L.d.W.);<email>amerongen@viroclinics.com</email> (G.v.A.)</nlm:aff></affiliation></author><author><name sortKey="Van Amerongen, Geert" sort="Van Amerongen, Geert" uniqKey="Van Amerongen G" first="Geert" last="Van Amerongen">Geert Van Amerongen</name><affiliation><nlm:aff id="af3-viruses-11-00381">Viroclinics Biosciences BV, Rotterdam 3029 AK, The Netherlands;<email>stittelaar@viroclinics.com</email> (K.J.S.);<email>dewaal@viroclinics.com</email> (L.d.W.);<email>amerongen@viroclinics.com</email> (G.v.A.)</nlm:aff></affiliation></author><author><name sortKey="Van Den Brand, Judith M A" sort="Van Den Brand, Judith M A" uniqKey="Van Den Brand J" first="Judith M. A." last="Van Den Brand">Judith M. A. Van Den Brand</name><affiliation><nlm:aff id="af1-viruses-11-00381">Department of Viroscience, Erasmus Medical Center, 3015GD Rotterdam, The Netherlands;<email>w.widagdo@erasmusmc.nl</email> (W.W.);<email>n.okba@erasmusmc.nl</email> (N.M.A.O.);<email>m.richard@erasmusmc.nl</email> (M.R.);<email>d.demeulder@erasmusmc.nl</email> (D.d.M.);<email>t.bestebroer@erasmusmc.nl</email> (T.M.B.);<email>p.lexmond@erasmusmc.nl</email> (P.L.);<email>j.m.a.vandenbrand@uu.nl</email> (J.M.A.v.d.B.);<email>s.herfst@erasmusmc.nl</email> (S.H.)</nlm:aff></affiliation></author><author><name sortKey="Haagmans, Bart L" sort="Haagmans, Bart L" uniqKey="Haagmans B" first="Bart L." last="Haagmans">Bart L. Haagmans</name><affiliation><nlm:aff id="af1-viruses-11-00381">Department of Viroscience, Erasmus Medical Center, 3015GD Rotterdam, The Netherlands;<email>w.widagdo@erasmusmc.nl</email> (W.W.);<email>n.okba@erasmusmc.nl</email> (N.M.A.O.);<email>m.richard@erasmusmc.nl</email> (M.R.);<email>d.demeulder@erasmusmc.nl</email> (D.d.M.);<email>t.bestebroer@erasmusmc.nl</email> (T.M.B.);<email>p.lexmond@erasmusmc.nl</email> (P.L.);<email>j.m.a.vandenbrand@uu.nl</email> (J.M.A.v.d.B.);<email>s.herfst@erasmusmc.nl</email> (S.H.)</nlm:aff></affiliation></author><author><name sortKey="Herfst, Sander" sort="Herfst, Sander" uniqKey="Herfst S" first="Sander" last="Herfst">Sander Herfst</name><affiliation><nlm:aff id="af1-viruses-11-00381">Department of Viroscience, Erasmus Medical Center, 3015GD Rotterdam, The Netherlands;<email>w.widagdo@erasmusmc.nl</email> (W.W.);<email>n.okba@erasmusmc.nl</email> (N.M.A.O.);<email>m.richard@erasmusmc.nl</email> (M.R.);<email>d.demeulder@erasmusmc.nl</email> (D.d.M.);<email>t.bestebroer@erasmusmc.nl</email> (T.M.B.);<email>p.lexmond@erasmusmc.nl</email> (P.L.);<email>j.m.a.vandenbrand@uu.nl</email> (J.M.A.v.d.B.);<email>s.herfst@erasmusmc.nl</email> (S.H.)</nlm:aff></affiliation></author></analytic><series><title level="j">Viruses</title><idno type="eISSN">1999-4915</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Middle East respiratory syndrome coronavirus (MERS-CoV) transmission from dromedaries to humans has resulted in major outbreaks in the Middle East. Although some other livestock animal species have been shown to be susceptible to MERS-CoV, it is not fully understood why the spread of the virus in these animal species has not been observed in the field. In this study, we used rabbits to further characterize the transmission potential of MERS-CoV. In line with the presence of MERS-CoV receptor in the rabbit nasal epithelium, high levels of viral RNA were shed from the nose following virus inoculation. However, unlike MERS-CoV-infected dromedaries, these rabbits did not develop clinical manifestations including nasal discharge and did shed only limited amounts of infectious virus from the nose. Consistently, no transmission by contact or airborne routes was observed in rabbits. Our data indicate that despite relatively high viral RNA levels produced, low levels of infectious virus are excreted in the upper respiratory tract of rabbits as compared to dromedary camels, thus resulting in a lack of viral transmission.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Zaki, A M" uniqKey="Zaki A">A.M. Zaki</name></author><author><name sortKey="Van Boheemen, S" uniqKey="Van Boheemen S">S. van Boheemen</name></author><author><name sortKey="Bestebroer, T M" uniqKey="Bestebroer T">T.M. Bestebroer</name></author><author><name sortKey="Osterhaus, A D" uniqKey="Osterhaus A">A.D. Osterhaus</name></author><author><name sortKey="Fouchier, R A" uniqKey="Fouchier R">R.A. Fouchier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Raj, V S" uniqKey="Raj V">V.S. Raj</name></author><author><name sortKey="Farag, E A" uniqKey="Farag E">E.A. 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A.</given-names></name><xref ref-type="aff" rid="af1-viruses-11-00381">1</xref><xref ref-type="author-notes" rid="fn1-viruses-11-00381">†</xref></contrib><contrib contrib-type="author"><name><surname>Richard</surname><given-names>Mathilde</given-names></name><xref ref-type="aff" rid="af1-viruses-11-00381">1</xref></contrib><contrib contrib-type="author"><name><surname>de Meulder</surname><given-names>Dennis</given-names></name><xref ref-type="aff" rid="af1-viruses-11-00381">1</xref></contrib><contrib contrib-type="author"><name><surname>Bestebroer</surname><given-names>Theo M.</given-names></name><xref ref-type="aff" rid="af1-viruses-11-00381">1</xref></contrib><contrib contrib-type="author"><name><surname>Lexmond</surname><given-names>Pascal</given-names></name><xref ref-type="aff" rid="af1-viruses-11-00381">1</xref></contrib><contrib contrib-type="author"><name><surname>Farag</surname><given-names>Elmoubasher A. B. A.</given-names></name><xref ref-type="aff" rid="af2-viruses-11-00381">2</xref></contrib><contrib contrib-type="author"><name><surname>Al-Hajri</surname><given-names>Mohammed</given-names></name><xref ref-type="aff" rid="af2-viruses-11-00381">2</xref></contrib><contrib contrib-type="author"><name><surname>Stittelaar</surname><given-names>Koert J.</given-names></name><xref ref-type="aff" rid="af3-viruses-11-00381">3</xref></contrib><contrib contrib-type="author"><name><surname>de Waal</surname><given-names>Leon</given-names></name><xref ref-type="aff" rid="af3-viruses-11-00381">3</xref></contrib><contrib contrib-type="author"><name><surname>van Amerongen</surname><given-names>Geert</given-names></name><xref ref-type="aff" rid="af3-viruses-11-00381">3</xref></contrib><contrib contrib-type="author"><name><surname>van den Brand</surname><given-names>Judith M. A.</given-names></name><xref ref-type="aff" rid="af1-viruses-11-00381">1</xref><xref ref-type="author-notes" rid="fn2-viruses-11-00381">‡</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0001-6221-2015</contrib-id><name><surname>Haagmans</surname><given-names>Bart L.</given-names></name><xref ref-type="aff" rid="af1-viruses-11-00381">1</xref><xref rid="c1-viruses-11-00381" ref-type="corresp">*</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0001-9866-8903</contrib-id><name><surname>Herfst</surname><given-names>Sander</given-names></name><xref ref-type="aff" rid="af1-viruses-11-00381">1</xref></contrib></contrib-group><aff id="af1-viruses-11-00381"><label>1</label>Department of Viroscience, Erasmus Medical Center, 3015GD Rotterdam, The Netherlands;<email>w.widagdo@erasmusmc.nl</email> (W.W.);<email>n.okba@erasmusmc.nl</email> (N.M.A.O.);<email>m.richard@erasmusmc.nl</email> (M.R.);<email>d.demeulder@erasmusmc.nl</email> (D.d.M.);<email>t.bestebroer@erasmusmc.nl</email> (T.M.B.);<email>p.lexmond@erasmusmc.nl</email> (P.L.);<email>j.m.a.vandenbrand@uu.nl</email> (J.M.A.v.d.B.);<email>s.herfst@erasmusmc.nl</email> (S.H.)</aff><aff id="af2-viruses-11-00381"><label>2</label>Ministry of Public Health, Doha, Qatar, PO Box. 42;<email>eabdfarag@MOPH.GOV.QA</email> (E.A.B.A.F.);<email>malhajri1@MOPH.GOV.QA</email> (M.A.-H.)</aff><aff id="af3-viruses-11-00381"><label>3</label>Viroclinics Biosciences BV, Rotterdam 3029 AK, The Netherlands;<email>stittelaar@viroclinics.com</email> (K.J.S.);<email>dewaal@viroclinics.com</email> (L.d.W.);<email>amerongen@viroclinics.com</email> (G.v.A.)</aff><author-notes><corresp id="c1-viruses-11-00381"><label>*</label>Correspondence: <email>b.haagmans@erasmusmc.nl</email>; Tel.: +31-10-704-4004; Fax: +31-10-704-4760</corresp><fn id="fn1-viruses-11-00381"><label>†</label><p>These authors contributed equally to this work.</p></fn><fn id="fn2-viruses-11-00381"><label>‡</label><p>Current address: Department of Pathobiology, Utrecht University, 3584CS Utrecht, The Netherlands.</p></fn></author-notes><pub-date pub-type="epub"><day>24</day><month>4</month><year>2019</year></pub-date><pub-date pub-type="collection"><month>4</month><year>2019</year></pub-date><volume>11</volume><issue>4</issue><elocation-id>381</elocation-id><history><date date-type="received"><day>18</day><month>3</month><year>2019</year></date><date date-type="accepted"><day>22</day><month>4</month><year>2019</year></date></history><permissions><copyright-statement>© 2019 by the authors.</copyright-statement><copyright-year>2019</copyright-year><license license-type="open-access"><license-p>Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>).</license-p></license></permissions><abstract><p>Middle East respiratory syndrome coronavirus (MERS-CoV) transmission from dromedaries to humans has resulted in major outbreaks in the Middle East. Although some other livestock animal species have been shown to be susceptible to MERS-CoV, it is not fully understood why the spread of the virus in these animal species has not been observed in the field. In this study, we used rabbits to further characterize the transmission potential of MERS-CoV. In line with the presence of MERS-CoV receptor in the rabbit nasal epithelium, high levels of viral RNA were shed from the nose following virus inoculation. However, unlike MERS-CoV-infected dromedaries, these rabbits did not develop clinical manifestations including nasal discharge and did shed only limited amounts of infectious virus from the nose. Consistently, no transmission by contact or airborne routes was observed in rabbits. Our data indicate that despite relatively high viral RNA levels produced, low levels of infectious virus are excreted in the upper respiratory tract of rabbits as compared to dromedary camels, thus resulting in a lack of viral transmission.</p></abstract><kwd-group><kwd>MERS-coronavirus</kwd><kwd>transmission</kwd><kwd>rabbits</kwd></kwd-group></article-meta></front><floats-group><fig id="viruses-11-00381-f001" orientation="portrait" position="float"><label>Figure 1</label><caption><p>Dipeptidyl peptidase-1 (DPP4) expression in the respiratory tract tissues of rabbits. DPP4 is detected using immunohistochemistry and indicated in red in the figure. Type II cells are indicated with arrows, and type I cells with an arrowhead. Nasal epithelium and bronchiolar epithelium pictures were taken at a 400× magnification, and alveolar epithelium at 1000×. The isotype control showed no background signal in our assay.</p></caption><graphic xlink:href="viruses-11-00381-g001"></graphic></fig><fig id="viruses-11-00381-f002" orientation="portrait" position="float"><label>Figure 2</label><caption><p>Middle East respiratory syndrome coronavirus (MERS-CoV) inoculation in rabbits with different routes and volumes. Three New Zealand rabbits were each infected either with (a) 200 µL of 1 × 10<sup>6</sup> TCID<sub>50</sub>/mL MERS-CoV intranasal (I.N.); (b) 1 mL of 1 × 10<sup>6</sup> TCID<sub>50</sub>/mL MERS-CoV I.N.; (c) 200 µL of 1 × 10<sup>6</sup> TCID<sub>50</sub>/mL MERS-CoV I.N. combined with 3 mL of 4 × 10<sup>6</sup> TCID<sub>50</sub>/mL MERS-CoV intratracheal (I.T.); or (d) 1mL of PBS I.N as negative control. These animals were sacrificed at day 4 post inoculation. Viral RNA shed by the MERS-CoV-inoculated rabbits in the nasal swabs (<bold>A</bold>) and throat swabs (<bold>B</bold>) are reported in genome equivalents per ml (GE/mL). Viral RNA detected in the lungs of these rabbits are reported in genome equivalents per gram tissues (GE/g). Dashed lines depict the detection limit of the assays. All error bars represent standard deviations. Statistical analysis is performed using Kruskal wallis test (**, <italic>p</italic> value < 0.01; ***, <italic>p</italic> value < 0.001). Representative figures of immunohistochemistry detecting MERS-CoV nucleoprotein (displayed in red) in the lungs of these rabbits were taken at a 200× magnification (<bold>D</bold>). All MERS-CoV-inoculated rabbits shed a relatively equal amount of viral RNA in the nasal and throat swabs (<bold>A</bold>,<bold>B</bold>). However, there was significantly less viral RNA in the lungs of rabbits in the group (a) in comparison to the other MERS-CoV-inoculated groups (<bold>C</bold>). A similar finding is observed in our immunohistochemistry analysis detecting MERS-CoV nucleoprotein (displayed in red) in the lungs of these rabbits (<bold>D</bold>). Pictures were taken in 200× magnification. The amount of viral RNA is displayed either in genome equivalent per mL (GE/mL) or per gram tissues (GE/g). Dashed lines depict the detection limit of the assays. All error bars represent standard deviations. Statistical analysis is performed using Kruskal–Wallis test (**, <italic>p</italic> value < 0.01; ***, <italic>p</italic> value < 0.001).</p></caption><graphic xlink:href="viruses-11-00381-g002"></graphic></fig><fig id="viruses-11-00381-f003" orientation="portrait" position="float"><label>Figure 3</label><caption><p>Middle East respiratory syndrome coronavirus (MERS-CoV) EMC strain and Qatar15 strain replicate equally in the upper respiratory tract of rabbits. Five New Zealand rabbits were each intranasally inoculated either with 1 mL of 1 × 10<sup>6</sup> TCID<sub>50</sub>/mL MERS-CoV EMC strain or Qatar15 strain. Nasal and throat swabs were obtained from day 0 (before inoculation) until day 4 post inoculation. The amount of viral RNA is displayed in genome equivalents per mL (GE/mL). Dashed lines depict the detection limit of the assay. All error bars represent standard deviations.</p></caption><graphic xlink:href="viruses-11-00381-g003"></graphic></fig><fig id="viruses-11-00381-f004" orientation="portrait" position="float"><label>Figure 4</label><caption><p>Middle East respiratory syndrome coronavirus (MERS-CoV) infects the upper and lower respiratory tract of Netherland dwarf rabbits. The amount of viral RNA in the nasal and throat swabs (<bold>A</bold>) as well as in the respiratory tract tissues (<bold>B</bold>) are displayed in genome equivalents per mL (GE/mL) and genome equivalents per gram tissues (GE/g), respectively. Dashed lines depict the detection limit of the assays. All error bars represent standard error of means.</p></caption><graphic xlink:href="viruses-11-00381-g004"></graphic></fig><fig id="viruses-11-00381-f005" orientation="portrait" position="float"><label>Figure 5</label><caption><p>Shedding of Middle East respiratory syndrome coronavirus (MERS-CoV) RNA and infectious virus in directly inoculated, contact-exposed and airborne-exposed rabbits. MERS-CoV RNA and infectious virus were measured in the nasal (<bold>A</bold>,<bold>B</bold>) and throat swabs (<bold>C</bold>,<bold>D</bold>). The amount of viral RNA is displayed in genome equivalents per mL (GE/mL), while infectious virus is shown as 50% tissue culture infective dose per ml (TCID<sub>50</sub>/mL). Dashed lines depict the detection limit of each assay.</p></caption><graphic xlink:href="viruses-11-00381-g005"></graphic></fig><fig id="viruses-11-00381-f006" orientation="portrait" position="float"><label>Figure 6</label><caption><p>Middle East respiratory syndrome coronavirus (MERS-CoV)-specific antibody response in rabbits. S1-specific MERS-CoV antibodies were measured with ELISA and displayed as optical density (OD) value (<bold>A</bold>), while MERS-CoV neutralizing antibodies were measured with the virus neutralization test (VNT) and displayed in titers (<bold>B</bold>). Dashed lines depict the detection limit of the assay.</p></caption><graphic xlink:href="viruses-11-00381-g006"></graphic></fig></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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