HIV-1 Nef mediates lymphocyte chemotaxis and activation by infected macrophages

S Swingler1, A Mann, J Jacqué

  • 1University of Massachusetts Medical Center, Program in Molecular Medicine, 373 Plantation Street, Worcester, Massachusetts 01605, USA.

Nature Medicine
|September 2, 1999
PubMed

Insights

The HIV-1 Nef protein induces macrophages to produce chemokines, attracting and activating T lymphocytes. This process facilitates further virus replication at infection sites.

Area of Science:

  • Virology
  • Immunology
  • Cell Biology

Background:

  • Primate lentiviruses, including HIV-1, infect macrophage lineage cells.
  • Viral properties often evolve to enhance macrophage infection and replication.

Purpose of the Study:

  • To investigate the role of the HIV-1 accessory gene product Nef in chemokine production by infected macrophages.
  • To determine if Nef-induced chemokines influence T lymphocyte behavior and subsequent HIV-1 infection.

Main Methods:

  • Demonstrated Nef's induction of macrophage inflammatory proteins 1-alpha and 1-beta (MIP-1α, MIP-1β) in HIV-1-infected macrophages.
  • Utilized adenovirus-mediated gene transfer to express Nef in primary macrophages.
  • Assessed the effect of supernatants from Nef-expressing macrophages on T lymphocyte chemotaxis and activation.

Main Results:

  • HIV-1 Nef protein directly induces the production of CC-chemokines MIP-1α and MIP-1β by macrophages.
  • Adenovirus-mediated Nef expression in macrophages was sufficient to trigger chemokine release.
  • Supernatants from Nef-expressing macrophages promoted T lymphocyte chemotaxis and activation, enabling productive HIV-1 infection.

Conclusions:

  • Nef plays a crucial role in recruiting and activating T lymphocytes to sites of HIV-1 replication.
  • Nef-mediated chemokine production contributes to the spread and propagation of HIV-1 infection by influencing lymphocyte availability and function.

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