Distinct Severe Acute Respiratory Syndrome Coronavirus-Induced Acute Lung Injury Pathways in Two Different Nonhuman Primate Species

Saskia Smits, Judith van den Brand, Anna Lang, Lonneke Leijten, Wilfred van Ijcken, Geert Amerongen, Ab Osterhaus, Arno Andeweg, Bart Haagmans

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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 1 beta (IL-1 beta), 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.
Original languageUndefined/Unknown
Pages (from-to)4234-4245
Number of pages12
JournalJournal of Virology
Issue number9
Publication statusPublished - 2011

Research programs

  • EMC MGC-02-13-02
  • EMC MM-04-27-01

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