The DOI matches its Crossref record; 67 of the 67 references it cites were found in a registry or an index.
Exacerbated Innate Host Response to SARS-CoV in Aged Non-Human Primates
Open accessAbstract
The emergence of viral respiratory pathogens with pandemic potential, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and influenza A H5N1, urges the need for deciphering their pathogenesis to develop new intervention strategies. SARS-CoV infection causes acute lung injury (ALI) that may develop into life-threatening acute respiratory distress syndrome (ARDS) with advanced age correlating positively with adverse disease outcome. The molecular pathways, however, that cause virus-induced ALI/ARDS in aged individuals are ill-defined. Here, we show that SARS-CoV-infected aged macaques develop more severe pathology than young adult animals, even though viral replication levels are similar. Comprehensive genomic analyses indicate that aged macaques have a stronger host response to virus infection than young adult macaques, with an increase in differential expression of genes associated with inflammation, with NF-kappaB as central player, whereas expression of type I interferon (IFN)-beta is reduced. Therapeutic treatment of SARS-CoV-infected aged macaques with type I IFN reduces pathology and diminishes pro-inflammatory gene expression, including interleukin-8 (IL-8) levels, without affecting virus replication in the lungs. Thus, ALI in SARS-CoV-infected aged macaques developed as a result of an exacerbated innate host response. The anti-inflammatory action of type I IFN reveals a potential intervention strategy for virus-induced ALI.
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Cited by
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Pathogenic T-cells and inflammatory monocytes incite inflammatory storms in severe COVID-19 patients
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Self-citation
Metadata
- Authors
- Smits, S. L., de Lang, A., van den Brand, J. M. A., Leijten, L. M., van IJcken, W. F., Eijkemans, M. J. C., van Amerongen, G., Kuiken, T., Andeweg, A. C., Osterhaus, A. D. M. E., & Haagmans, B. L.
- Venue
- PLoS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2010-02-05
- Volume
- 6
- Issue
- 2
- Pages
- e1000756
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- OpenAlex
- W1984064716
- Cited by
- 335
- References
- 67
- FWCI
- 6.53
- Type
- journal article
- Language
- en
- Open access
- gold
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- Smits, S. L., de Lang, A., van den Brand, J. M. A., Leijten, L. M., van IJcken, W. F., Eijkemans, M. J. C., van Amerongen, G., Kuiken, T., Andeweg, A. C., Osterhaus, A. D. M. E., & Haagmans, B. L. (2010). Exacerbated Innate Host Response to SARS-CoV in Aged Non-Human Primates. PLoS Pathogens. https://doi.org/10.1371/journal.ppat.1000756
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