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Updated: Jun 12, 2026

Peptide-based Identification of Functional Motifs and their Binding Partners
Published on: July 1, 2013
HIV-1 Nef mediates lymphocyte chemotaxis and activation by infected macrophages
1University of Massachusetts Medical Center, Program in Molecular Medicine, 373 Plantation Street, Worcester, Massachusetts 01605, USA.
Abstract:
Infection of macrophage lineage cells is a feature of primate lentivirus replication, and several properties of primate lentiviruses seem to have evolved to promote the infection of macrophages. Here we demonstrate that the accessory gene product Nef induces the production of two CC-chemokines, macrophage inflammatory proteins 1alpha and 1beta, by HIV-1-infected macrophages. Adenovirus-mediated expression of Nef in primary macrophages was sufficient for chemokine induction. Supernatants from Nef-expressing macrophages induced both the chemotaxis and activation of resting T lymphocytes, permitting productive HIV-1 infection. These results indicate a role for Nef in lymphocyte recruitment and activation at sites of virus replication.
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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