Related Experiment Video

Updated: Aug 28, 2025

Production of Pseudotyped Particles to Study Highly Pathogenic Coronaviruses in a Biosafety Level 2 Setting
08:40

Production of Pseudotyped Particles to Study Highly Pathogenic Coronaviruses in a Biosafety Level 2 Setting

Published on: March 1, 2019

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Autophagy-linked plasma and lysosomal membrane protein PLAC8 is a key host factor for SARS-CoV-2 entry into human

Alejandro P Ugalde1, Gabriel Bretones1, David Rodríguez1,2

  • 1Departamento de Bioquímica y Biología Molecular, Instituto Universitario de Oncología (IUOPA), Universidad de Oviedo, Oviedo, Spain.

The EMBO Journal
|September 20, 2022
PubMed

Insights

Researchers identified two new host factors, SPNS1 and PLAC8, crucial for SARS-CoV-2 entry and COVID-19 pathology. Understanding these interactions aids in developing targeted therapies against the virus.

Area of Science:

  • Virology
  • Cell Biology
  • Genetics

Background:

  • Understanding host-pathogen interactions is key to combating SARS-CoV-2 infections and COVID-19.
  • Identifying host factors involved in viral entry can reveal potential therapeutic targets.

Purpose of the Study:

  • To identify novel host factors involved in SARS-CoV-2 infection using a genome-wide screen.
  • To investigate the role of identified factors in viral entry and pathogenesis.

Main Methods:

  • Genome-wide CRISPR/Cas9 loss-of-function screen using SARS-CoV-2-pseudotyped lentiviruses.
  • Functional experiments with full SARS-CoV-2 viruses.
  • Single-cell RNA-Seq, proteomics, and cell biology studies.

Main Results:

  • Two novel host factors, SPNS1 and PLAC8, were identified as critical for SARS-CoV-2 entry.
  • Loss-of-function of SPNS1 and PLAC8 impairs viral entry.
  • PLAC8 is a limiting host factor that enhances viral infection when overexpressed.
  • PLAC8 is highly expressed in susceptible respiratory and gut cell types.
  • SPNS1 and PLAC8 regulate the autophagolysosomal compartment and virion fate.

Conclusions:

  • SPNS1 and PLAC8 are critical host factors for SARS-CoV-2 infection.
  • These factors influence viral entry and intracellular trafficking.
  • Targeting SPNS1 and PLAC8 may offer new strategies for COVID-19 treatment.
Keywords:
autophagycovid19genetic screenplac8spns1

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