Analysis of innate immune sensing of SARS-CoV-2 using recombinant viruses

  • Funded by Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF)
  • Total publications:2 publications

Grant number: 01KI20172A

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Key facts

  • Disease

    COVID-19
  • Start & end year

    2020
    2021
  • Known Financial Commitments (USD)

    $496,512.22
  • Funder

    Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF)
  • Principle Investigator

    Pending
  • Research Location

    Germany, Europe
  • Lead Research Institution

    Friedrich-Alexander-Universität Erlangen-Nürnberg
  • Research Category

    Pathogen: natural history, transmission and diagnostics

  • Research Subcategory

    Immunity

  • Special Interest Tags

    Gender

  • Study Subject

    Non-Clinical

  • Clinical Trial Details

    N/A

  • Broad Policy Alignment

    Pending

  • Age Group

    Not Applicable

  • Vulnerable Population

    Not applicable

  • Occupations of Interest

    Not applicable

Abstract

discovery - The fast pandemic spread of SARS-CoV-2 is fostered by its rather high reproduction number R0 but also by a significant proportion of oligo- or asymptomatic infections that complicate containment. The circumstance that the virus is able to replicate without notable signs of inflammation suggests that the initial innate immune control of viral replication might be deregulated and less effective. Thus, this study aims at characterizing mechanisms that allow SARS-CoV-2 to evade innate immune sensing by the host. Proteins in CoVs that counteract immune sensing include the Endonuclease U (Nsp15) and 2OMethyltransferase (Nsp16), which inhibit the detection of CoV RNA by host RNA sensors upon infection. In addition, mutations in the accessory protein ORF8 have been linked to a reduced replication of SARS-CoV. Here, we will analyze the effects of these immunomodulatory factors in shielding SARS-CoV-2 from innate immunity by generating recombinant viruses lacking the respective functional ORFs. We will test the replication capacity and the ability to avoid detection by innate immunity in vitro and in vivo using transgenic human ACE-2 mice. Making the virus more "visible" to intrinsic immunity will allow the immune system to better control viral replication and clear the virus more efficiently. Identifying viral proteins, which inhibit innate sensing of SARS-CoV-2, will be of high interest to both vaccine development and therapy.

Publicationslinked via Europe PMC

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ORF3c is expressed in SARS-CoV-2-infected cells and inhibits innate sensing by targeting MAVS.

Nsp16 shields SARS-CoV-2 from efficient MDA5 sensing and IFIT1-mediated restriction.