Document Detail


Distinct severe acute respiratory syndrome coronavirus-induced acute lung injury pathways in two different nonhuman primate species.
MedLine Citation:
PMID:  21325418     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), caused by influenza A virus H5N1 and severe acute respiratory syndrome coronavirus (SARS-CoV), supposedly depend on activation of the oxidative-stress machinery that is coupled with innate immunity, resulting in a strong proinflammatory host response. Inflammatory cytokines, such as interleukin 1β (IL-1β), IL-8, and IL-6, play a major role in mediating and amplifying ALI/ARDS by stimulating chemotaxis and activation of neutrophils. To obtain further insight into the pathogenesis of SARS-CoV-associated ALI, we compared SARS-CoV infections in two different nonhuman primate species, cynomolgus macaques and African green monkeys. Viral titers in the upper and lower respiratory tract were not significantly different in SARS-CoV-infected macaques and African green monkeys. Inflammatory cytokines that play a major role in mediating and amplifying ALI/ARDS or have neutrophil chemoattractant activity, such as IL-6, IL-8, CXCL1, and CXCL2, were, however, induced only in macaques. In contrast, other proinflammatory cytokines and chemokines, including osteopontin and CCL3, were upregulated in the lungs of African green monkeys to a significantly greater extent than in macaques. Because African green monkeys developed more severe ALI than macaques, with hyaline membrane formation, some of these differentially expressed proinflammatory genes may be critically involved in development of the observed pathological changes. Induction of distinct proinflammatory genes after SARS-CoV infection in different nonhuman primate species needs to be taken into account when analyzing outcomes of intervention strategies in these species.
Authors:
Saskia L Smits; Judith M A van den Brand; Anna de Lang; Lonneke M E Leijten; Wilfred F van Ijcken; Geert van Amerongen; Albert D M E Osterhaus; Arno C Andeweg; Bart L Haagmans
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-02-16
Journal Detail:
Title:  Journal of virology     Volume:  85     ISSN:  1098-5514     ISO Abbreviation:  J. Virol.     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-04-18     Completed Date:  2011-06-14     Revised Date:  2011-11-01    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4234-45     Citation Subset:  IM    
Affiliation:
Department of Virology, Erasmus Medical Center, P.O. Box 2040, 3000 CA Rotterdam, Netherlands. s.smits@erasmusmc.nl
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MeSH Terms
Descriptor/Qualifier:
Acute Lung Injury / pathology*
Animals
Cercopithecus aethiops
Cytokines / secretion
Lung / immunology,  pathology
Macaca fascicularis
Primate Diseases / pathology*,  virology*
Respiratory Distress Syndrome, Adult / pathology*
Respiratory System / virology
SARS Virus / pathogenicity*
Severe Acute Respiratory Syndrome / pathology*,  virology*
Viral Load
Grant Support
ID/Acronym/Agency:
HL080621-01A1/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Cytokines

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