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HIV-1 restriction by SERINC5.

Lucía Cano-Ortiz1,2, Tom Luedde1, Carsten Münk3

  • 1Clinic for Gastroenterology, Hepatology, and Infectiology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Building 23.12.U1.82, Moorenstr. 5, 40225, Düsseldorf, Germany.

Medical Microbiology and Immunology
|March 25, 2022
PubMed
Summary
This summary is machine-generated.

Serine incorporator 5 (SERINC5) restricts human immunodeficiency virus 1 (HIV-1) entry by disrupting viral membrane fusion. However, HIV-1’s Nef protein counteracts this restriction by downregulating SER5.

Keywords:
HIV-1NefRestriction factorsSERINC5

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Area of Science:

  • Virology
  • Cell Biology
  • Immunology

Background:

  • Serine incorporator 5 (SERINC5) is a transmembrane protein with incompletely understood cellular functions.
  • SER5 acts as a restriction factor against human immunodeficiency virus 1 (HIV-1) lacking the Nef accessory protein.
  • SER5 incorporation into the viral membrane inhibits HIV-1 entry by disrupting viral and plasma membrane fusion.

Purpose of the Study:

  • To review the current understanding of SER5's role in restricting HIV-1.
  • To explore the mechanisms by which SER5 inhibits viral fusion.
  • To discuss viral evasion strategies and SER5's broader role in innate immunity.

Main Methods:

  • Literature review of studies on SER5 and HIV-1 interaction.
  • Analysis of viral mechanisms for SER5 evasion.
  • Examination of SER5's function in innate signaling pathways.

Main Results:

  • SER5 inhibits HIV-1 (Δ Nef) entry by impairing viral-plasma membrane fusion.
  • Viral envelope proteins can escape SER5-mediated restriction.
  • Primate lentiviruses, including HIV-1 and SIVs, utilize Nef to downregulate SER5 via endocytosis.
  • SER5 also functions as an adapter protein in innate immune signaling, inducing inflammatory cytokines.

Conclusions:

  • SER5 is a key intrinsic antiviral factor against HIV-1, primarily by blocking membrane fusion.
  • Viral Nef protein is crucial for overcoming SER5 restriction, highlighting a viral counter-defense mechanism.
  • SER5's dual role in direct viral restriction and innate immune signaling underscores its significance in host defense.