Cynomolgus Macaque as an Animal Model for Severe Acute Respiratory Syndrome

Lawler, James V.; Endy, Timothy P.; Hensley, Lisa E.; Garrison, Aura; Fritz, Elizabeth A.; Lesar, May; Baric, Ralph S.; Kulesh, David A.; Norwood, David A.; Wasieloski, Leonard P.; Ulrich, Melanie P.; Slezak, Tom R.; Vitalis, Elizabeth; Huggins, John W.; Jahrling, Peter B.; Paragas, Jason

doi:10.1371/journal.pmed.0030149

Cynomolgus Macaque as an Animal Model for Severe Acute Respiratory Syndrome

Journal Article · Tue Apr 18 00:00:00 EDT 2006 · PLoS Medicine

DOI:https://doi.org/10.1371/journal.pmed.0030149· OSTI ID:1627323

Lawler, James V. ^[1]; Endy, Timothy P. ^[2]; Hensley, Lisa E. ^[2]; Garrison, Aura ^[2]; Fritz, Elizabeth A. ^[2]; Lesar, May ^[3]; Baric, Ralph S. ^[4]; Kulesh, David A. ^[2]; Norwood, David A. ^[2]; Wasieloski, Leonard P. ^[2]; Ulrich, Melanie P. ^[2]; Slezak, Tom R. ^[5]; Vitalis, Elizabeth ^[5]; Huggins, John W. ^[2]; Jahrling, Peter B. ^[2]; Paragas, Jason ^[2]

National Naval Medical Center (NNMC), Bethesda, MD (United States); DOE/OSTI
United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD (United States)
National Naval Medical Center (NNMC), Bethesda, MD (United States)
Univ. of North Carolina, Chapel Hill, NC (United States). Dept. of Epidemiology
Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)

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 post-infection. 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.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)

Sponsoring Organization:: Department of the Army; National Institute of Allergy and Infectious Diseases; National Institutes of Health (NIH); USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC52-07NA27344

OSTI ID:: 1627323

Journal Information:: PLoS Medicine, Journal Name: PLoS Medicine Journal Issue: 5 Vol. 3; ISSN 1549-1676

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
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