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TIP47 is required for the production of infectious HIV-1 particles from primary macrophages

Hélène Bauby1, Sandra Lopez-Vergès, Guillaume Hoeffel

  • 1Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Paris, France.

Traffic (Copenhagen, Denmark)
|January 15, 2010
PubMed

Insights

The cellular cofactor TIP47 is essential for human immunodeficiency virus type 1 (HIV-1) production in macrophages. TIP47 (also known as?’”LDLRAD3”) facilitates the crucial encounter between Gag and Env proteins, enabling the generation of infectious HIV-1 particles.

Area of Science:

  • * Virology
  • * Immunology
  • * Cell Biology

Background:

  • * Macrophages are key targets and reservoirs for human immunodeficiency virus type 1 (HIV-1).
  • * Understanding cellular cofactors is vital for controlling HIV-1 pathogenesis and replication.
  • * Identifying factors that mediate HIV-1 production in macrophages is crucial.

Purpose of the Study:

  • * To investigate the role of the cellular cofactor TIP47 in HIV-1 morphogenesis and infectivity in primary macrophages.
  • * To determine how TIP47 influences the interaction between HIV-1 Gag and Env proteins.
  • * To elucidate the mechanism by which TIP47 contributes to the generation of infectious HIV-1.

Main Methods:

  • * Utilized siRNA to deplete TIP47 in primary human macrophages.
  • * Analyzed HIV-1 infectivity and propagation.
  • * Investigated the colocalization of HIV-1 Gag and Env proteins using microscopy.
  • * Employed coimmunoprecipitation assays to study protein interactions.
  • * Introduced mutations in HIV-1 Gag and Env to disrupt TIP47 interaction.

Main Results:

  • * TIP47 depletion significantly impairs HIV-1 infectivity and propagation.
  • * TIP47 silencing disrupts the colocalization of Gag and Env proteins within macrophages.
  • * Mutations abolishing Gag-TIP47 or Env-TIP47 interactions reduce viral propagation and infectivity.
  • * Disruption of Gag-TIP47 interaction leads to aberrant Gag localization near the plasma membrane.
  • * TIP47 is essential for the necessary encounter between Gag and Env for viral assembly.

Conclusions:

  • * TIP47 is a critical cellular cofactor for the production of infectious HIV-1 in macrophages.
  • * TIP47 mediates the essential interaction between HIV-1 Gag and Env proteins.
  • * Targeting TIP47 could be a potential strategy to inhibit HIV-1 replication in macrophages.

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