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Viruses 2013, 5(9), 2235-2252; doi:10.3390/v5092235
Article

HIV-1 Infection of T Cells and Macrophages Are Differentially Modulated by Virion-Associated Hck: A Nef-Dependent Phenomenon

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Received: 27 May 2013 / Revised: 1 September 2013 / Accepted: 12 September 2013 / Published: 18 September 2013
(This article belongs to the Section Viruses of Plants, Fungi and Protoza)
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Abstract

The proline repeat motif (PxxP) of Nef is required for interaction with the SH3 domains of macrophage-specific Src kinase Hck. However, the implication of this interaction for viral replication and infectivity in macrophages and T lymphocytes remains unclear. Experiments in HIV-1 infected macrophages confirmed the presence of a Nef:Hck complex which was dependent on the Nef proline repeat motif. The proline repeat motif of Nef also enhanced both HIV-1 infection and replication in macrophages, and was required for incorporation of Hck into viral particles. Unexpectedly, wild-type Hck inhibited infection of macrophages, but Hck was shown to enhance infection of primary T lymphocytes. These results indicate that the interaction between Nef and Hck is important for Nef-dependent modulation of viral infectivity. Hck-dependent enhancement of HIV-1 infection of T cells suggests that Nef-Hck interaction may contribute to the spread of HIV-1 infection from macrophages to T cells by modulating events in the producer cell, virion and target cell.
Keywords: HIV-1; Nef; Hck; macrophage; T lymphocyte; virion; infectivity HIV-1; Nef; Hck; macrophage; T lymphocyte; virion; infectivity
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Cornall, A.; Mak, J.; Greenway, A.; Tachedjian, G. HIV-1 Infection of T Cells and Macrophages Are Differentially Modulated by Virion-Associated Hck: A Nef-Dependent Phenomenon. Viruses 2013, 5, 2235-2252.

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