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  1. Home
  3. Exacerbated Innate Host Response To Sars-cov In Aged Non-human Primates.
  1. Home
  3. Exacerbated Innate Host Response To Sars-cov In Aged Non-human Primates.

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Exacerbated innate host response to SARS-CoV in aged non-human primates.

Saskia L Smits1, Anna de Lang, Judith M A van den Brand

  • 1Department of Virology, Erasmus Medical Center, Rotterdam, The Netherlands.

Plos Pathogens
|February 9, 2010

View abstract on PubMed

Summary
This summary is machine-generated.

Aged macaques infected with SARS-CoV show severe lung injury due to heightened inflammation. Type I interferon therapy reduced this inflammation, offering a potential strategy against virus-induced acute lung injury (ALI).

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Area of Science:

  • Virology
  • Immunology
  • Gerontology

Background:

  • Viral respiratory pathogens like SARS-CoV pose pandemic threats, necessitating understanding of disease mechanisms.
  • Aging is linked to worse outcomes in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), but underlying molecular pathways are unclear.
  • SARS-CoV infection in aged individuals can lead to severe ALI/ARDS.

Purpose of the Study:

  • To investigate the molecular mechanisms of SARS-CoV-induced ALI in aged individuals.
  • To compare the host response to SARS-CoV infection in aged versus young macaques.
  • To evaluate type I interferon (IFN) as a therapeutic intervention for virus-induced ALI in aged subjects.

Main Methods:

  • SARS-CoV infection model in aged and young adult macaques.
  • Comprehensive genomic analyses to assess host gene expression.
  • Therapeutic administration of type I IFN in infected aged macaques.

    • Main Results:

    • Aged macaques exhibited more severe lung pathology than young macaques, despite similar viral loads.
    • Genomic analysis revealed an exacerbated inflammatory response in aged macaques, characterized by increased NF-kappaB activity and reduced type I IFN-beta expression.
    • Type I IFN treatment in aged macaques reduced lung pathology and pro-inflammatory gene expression (e.g., IL-8) without impacting viral replication.

    Conclusions:

    • Exacerbated innate host response, driven by inflammation, underlies severe ALI in aged SARS-CoV-infected macaques.
    • Type I interferon demonstrates anti-inflammatory properties and represents a potential therapeutic strategy for virus-induced ALI, particularly in aged populations.
    • Understanding age-related immune responses is crucial for developing effective interventions against emerging viral threats.