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Communicable diseases

HIV-1 Core Maturation Crucial for Fusion Capacity with Target Cells

Strategic Insights

— 1 min read

Virologists at Vanderbilt University, Tennessee, have shed light on the limited cell fusion capacity of HIV-1 until core maturation. They identified a link between HIV-1 core maturation and the virus' ability to fuse with target cells, demonstrating that immature HIV-1 particles are 5- to 10-fold less active in fusion than mature virions. The researchers propose a mechanism where the cleavage of Gag at specific sites activates HIV-1 fusion competence, preventing the entry of immature, noninfectious particles.

Key Takeaways:

  • HIV-1 core maturation is essential for the virus' ability to fuse with target cells, with immature particles being 5- to 10-fold less active in fusion than mature virions.
  • The gp41 cytoplasmic domain and glycoprotein of vesicular stomatitis virus are involved in regulating HIV-1 fusion competence.
  • Cleavage of Gag at specific sites between the MA and NC segments activates HIV-1 fusion competence, rendering mature and immature virions equivalent in fusion activity.
  • The 'inside-out' regulation of HIV-1 fusion inhibits membrane fusion on the surface of the virion, preventing the entry of immature, noninfectious particles.
  • This mechanism could play an important role in the HIV-1 life cycle, highlighting the significance of core maturation in viral infection.
  • The research was published in the Journal of Virology, highlighting the collaboration between D.J. Wyma and colleagues at Vanderbilt University.

Statistics:

  • Immature HIV-1 particles are 5- to 10-fold less active in fusion than mature virions.
  • The fusion of mature and immature virions was rendered equivalent by truncating the gp41 cytoplasmic domain or by pseudotyping viruses with the glycoprotein of vesicular stomatitis virus.
  • A panel of mutants containing mutated cleavage sites showed that HIV-1 fusion competence is activated by the cleavage of Gag at any site between the MA and NC segments.

Sources:

  • D.J. Wyma, et al. "Coupling of human immunodeficiency virus type 1 fusion to virion maturation: a novel role of the gp41 cytoplasmic tail." Journal of Virology, 2004;78(7):3429-3435.

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