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Stages of infection describe what happens to a susceptible host once a pathogen invades the human body. The stages of infection are incubation, prodromal, illness, stage of decline, and convalescence. The incubation stage is the period from exposure to a pathogen until symptoms start. The infected person is unaware of impending illness as the pathogens grow and multiply within the body. The duration may vary depending on the type of infection. The incubation period of measles averages ten to...
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Natural flora, body system defenses, and inflammation are natural barriers of the body against infectious agents regardless of previous exposure. Normal floras of the human body refer to the microbial population that colonizes the skin and mucous membranes.
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MERS-CoV Accessory ORFs Play Key Role for Infection and Pathogenesis.

Vineet D Menachery1,2, Hugh D Mitchell3, Adam S Cockrell2

  • 1Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.

Mbio
|August 24, 2017
PubMed
Summary
This summary is machine-generated.

Middle East respiratory syndrome coronavirus (MERS-CoV) accessory open reading frames (ORFs) are crucial for pathogenesis. Deleting these ORFs attenuates the virus, offering a potential live attenuated vaccine platform.

Keywords:
MERS-CoVSARS-CoVcoronaviruslive vector vaccinesreverse genetics

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Area of Science:

  • Virology
  • Immunology
  • Pathogenesis

Background:

  • Coronaviruses (CoVs) possess accessory open reading frame (ORF) proteins that, while not essential for replication, significantly impact infection and disease.
  • Middle East respiratory syndrome coronavirus (MERS-CoV) outbreaks pose a global public health threat, necessitating research into its pathogenesis.

Purpose of the Study:

  • To investigate the role of MERS-CoV accessory ORFs (ORF3, -4a, -4b, and -5) in viral pathogenesis and replication.
  • To evaluate the potential of a MERS-CoV mutant lacking these accessory ORFs as a live attenuated vaccine.

Main Methods:

  • Generation and characterization of a MERS-CoV mutant lacking all four accessory ORFs (dORF3-5).
  • Assessment of viral replication and host responses *in vitro* and *in vivo*.
  • Analysis of the role of ORF5 in modulating host inflammatory pathways, specifically NF-κB.

Main Results:

  • The absence of MERS-CoV accessory ORFs (dORF3-5) significantly impairs viral replication and pathogenesis.
  • Viral attenuation is primarily due to dysregulated host responses, including disrupted cellular processes, enhanced interferon pathway activation, and inflammation.
  • The dORF3-5 mutant demonstrated *in vitro* and *in vivo* replication attenuation, supporting its use as a vaccine platform.
  • ORF5 was found to play a partial role in modulating NF-κB-mediated inflammation.

Conclusions:

  • MERS-CoV accessory ORFs are critical for pathogenesis, not just viral replication.
  • The dORF3-5 mutant serves as a promising live attenuated vaccine candidate for MERS-CoV and related CoVs.
  • Targeting accessory ORFs offers potential therapeutic strategies and a rapid response platform for future emergent coronavirus strains.