Cynomolgus macaque as an animal model for severe acute respiratory syndrome.

The emergence of severe acute respiratory syndrome (SARS) in 2002 and 2003 affected global health and caused major economic disruption. Adequate animal models are required to study the underlying pathogenesis of SARS-associated coronavirus (SARS-CoV) infection and to develop effective vaccines and t...

Full description

Bibliographic Details
Main Authors: James V Lawler, Timothy P Endy, Lisa E Hensley, Aura Garrison, Elizabeth A Fritz, May Lesar, Ralph S Baric, David A Kulesh, David A Norwood, Leonard P Wasieloski, Melanie P Ulrich, Tom R Slezak, Elizabeth Vitalis, John W Huggins, Peter B Jahrling, Jason Paragas
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2006-05-01
Series:PLoS Medicine
Online Access:http://europepmc.org/articles/PMC1435788?pdf=render
_version_ 1819009705466396672
author James V Lawler
Timothy P Endy
Lisa E Hensley
Aura Garrison
Elizabeth A Fritz
May Lesar
Ralph S Baric
David A Kulesh
David A Norwood
Leonard P Wasieloski
Melanie P Ulrich
Tom R Slezak
Elizabeth Vitalis
John W Huggins
Peter B Jahrling
Jason Paragas
author_facet James V Lawler
Timothy P Endy
Lisa E Hensley
Aura Garrison
Elizabeth A Fritz
May Lesar
Ralph S Baric
David A Kulesh
David A Norwood
Leonard P Wasieloski
Melanie P Ulrich
Tom R Slezak
Elizabeth Vitalis
John W Huggins
Peter B Jahrling
Jason Paragas
author_sort James V Lawler
collection DOAJ
description The emergence of severe acute respiratory syndrome (SARS) in 2002 and 2003 affected global health and caused major economic disruption. Adequate animal models are required to study the underlying pathogenesis of SARS-associated coronavirus (SARS-CoV) infection and to develop effective vaccines and therapeutics. We report the first findings of measurable clinical disease in nonhuman primates (NHPs) infected with SARS-CoV.In order to characterize clinically relevant parameters of SARS-CoV infection in NHPs, we infected cynomolgus macaques with SARS-CoV in three groups: Group I was infected in the nares and bronchus, group II in the nares and conjunctiva, and group III intravenously. Nonhuman primates in groups I and II developed mild to moderate symptomatic illness. All NHPs demonstrated evidence of viral replication and developed neutralizing antibodies. Chest radiographs from several animals in groups I and II revealed unifocal or multifocal pneumonia that peaked between days 8 and 10 postinfection. Clinical laboratory tests were not significantly changed. Overall, inoculation by a mucosal route produced more prominent disease than did intravenous inoculation. Half of the group I animals were infected with a recombinant infectious clone SARS-CoV derived from the SARS-CoV Urbani strain. This infectious clone produced disease indistinguishable from wild-type Urbani strain.SARS-CoV infection of cynomolgus macaques did not reproduce the severe illness seen in the majority of adult human cases of SARS; however, our results suggest similarities to the milder syndrome of SARS-CoV infection characteristically seen in young children.
first_indexed 2024-12-21T01:00:37Z
format Article
id doaj.art-09f0c2a62c5246ed8f496a27737d02b1
institution Directory Open Access Journal
issn 1549-1277
1549-1676
language English
last_indexed 2024-12-21T01:00:37Z
publishDate 2006-05-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS Medicine
spelling doaj.art-09f0c2a62c5246ed8f496a27737d02b12022-12-21T19:21:11ZengPublic Library of Science (PLoS)PLoS Medicine1549-12771549-16762006-05-0135e14910.1371/journal.pmed.0030149Cynomolgus macaque as an animal model for severe acute respiratory syndrome.James V LawlerTimothy P EndyLisa E HensleyAura GarrisonElizabeth A FritzMay LesarRalph S BaricDavid A KuleshDavid A NorwoodLeonard P WasieloskiMelanie P UlrichTom R SlezakElizabeth VitalisJohn W HugginsPeter B JahrlingJason ParagasThe emergence of severe acute respiratory syndrome (SARS) in 2002 and 2003 affected global health and caused major economic disruption. Adequate animal models are required to study the underlying pathogenesis of SARS-associated coronavirus (SARS-CoV) infection and to develop effective vaccines and therapeutics. We report the first findings of measurable clinical disease in nonhuman primates (NHPs) infected with SARS-CoV.In order to characterize clinically relevant parameters of SARS-CoV infection in NHPs, we infected cynomolgus macaques with SARS-CoV in three groups: Group I was infected in the nares and bronchus, group II in the nares and conjunctiva, and group III intravenously. Nonhuman primates in groups I and II developed mild to moderate symptomatic illness. All NHPs demonstrated evidence of viral replication and developed neutralizing antibodies. Chest radiographs from several animals in groups I and II revealed unifocal or multifocal pneumonia that peaked between days 8 and 10 postinfection. Clinical laboratory tests were not significantly changed. Overall, inoculation by a mucosal route produced more prominent disease than did intravenous inoculation. Half of the group I animals were infected with a recombinant infectious clone SARS-CoV derived from the SARS-CoV Urbani strain. This infectious clone produced disease indistinguishable from wild-type Urbani strain.SARS-CoV infection of cynomolgus macaques did not reproduce the severe illness seen in the majority of adult human cases of SARS; however, our results suggest similarities to the milder syndrome of SARS-CoV infection characteristically seen in young children.http://europepmc.org/articles/PMC1435788?pdf=render
spellingShingle James V Lawler
Timothy P Endy
Lisa E Hensley
Aura Garrison
Elizabeth A Fritz
May Lesar
Ralph S Baric
David A Kulesh
David A Norwood
Leonard P Wasieloski
Melanie P Ulrich
Tom R Slezak
Elizabeth Vitalis
John W Huggins
Peter B Jahrling
Jason Paragas
Cynomolgus macaque as an animal model for severe acute respiratory syndrome.
PLoS Medicine
title Cynomolgus macaque as an animal model for severe acute respiratory syndrome.
title_full Cynomolgus macaque as an animal model for severe acute respiratory syndrome.
title_fullStr Cynomolgus macaque as an animal model for severe acute respiratory syndrome.
title_full_unstemmed Cynomolgus macaque as an animal model for severe acute respiratory syndrome.
title_short Cynomolgus macaque as an animal model for severe acute respiratory syndrome.
title_sort cynomolgus macaque as an animal model for severe acute respiratory syndrome
url http://europepmc.org/articles/PMC1435788?pdf=render
work_keys_str_mv AT jamesvlawler cynomolgusmacaqueasananimalmodelforsevereacuterespiratorysyndrome
AT timothypendy cynomolgusmacaqueasananimalmodelforsevereacuterespiratorysyndrome
AT lisaehensley cynomolgusmacaqueasananimalmodelforsevereacuterespiratorysyndrome
AT auragarrison cynomolgusmacaqueasananimalmodelforsevereacuterespiratorysyndrome
AT elizabethafritz cynomolgusmacaqueasananimalmodelforsevereacuterespiratorysyndrome
AT maylesar cynomolgusmacaqueasananimalmodelforsevereacuterespiratorysyndrome
AT ralphsbaric cynomolgusmacaqueasananimalmodelforsevereacuterespiratorysyndrome
AT davidakulesh cynomolgusmacaqueasananimalmodelforsevereacuterespiratorysyndrome
AT davidanorwood cynomolgusmacaqueasananimalmodelforsevereacuterespiratorysyndrome
AT leonardpwasieloski cynomolgusmacaqueasananimalmodelforsevereacuterespiratorysyndrome
AT melaniepulrich cynomolgusmacaqueasananimalmodelforsevereacuterespiratorysyndrome
AT tomrslezak cynomolgusmacaqueasananimalmodelforsevereacuterespiratorysyndrome
AT elizabethvitalis cynomolgusmacaqueasananimalmodelforsevereacuterespiratorysyndrome
AT johnwhuggins cynomolgusmacaqueasananimalmodelforsevereacuterespiratorysyndrome
AT peterbjahrling cynomolgusmacaqueasananimalmodelforsevereacuterespiratorysyndrome
AT jasonparagas cynomolgusmacaqueasananimalmodelforsevereacuterespiratorysyndrome