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


RESULTS
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.


CONCLUSIONS
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.
Lawler
James V
JV
Infectious Diseases Department, National Naval Medical Center, Bethesda, Maryland, United States of America.
Endy
Timothy P
TP
Hensley
Lisa E
LE
Garrison
Aura
A
Fritz
Elizabeth A
EA
Lesar
May
M
Baric
Ralph S
RS
Kulesh
David A
DA
Norwood
David A
DA
Wasieloski
Leonard P
LP
Ulrich
Melanie P
MP
Slezak
Tom R
TR
Vitalis
Elizabeth
E
Huggins
John W
JW
Jahrling
Peter B
PB
Paragas
Jason
J
D000818:Animals; D000917:Antibody Formation; D002675:Child, Preschool; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008252:Macaca fascicularis / Q000821:virology*; D008297:Male; D009092:Mucous Membrane / Q000821:virology; D045473:Severe acute respiratory syndrome-related coronavirus / Q000472:pathogenicity* / Q000502:physiology; D045169:Severe Acute Respiratory Syndrome / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology* / Q000517:prevention & control; D012720:Severity of Illness Index; D013577:Syndrome; D014612:Vaccines; D014779:Virus Replication
D014612:Vaccines