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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

1,2,3
,
4,5
,
1
 and
1,6,7,*
1 Centre for Biomedical Research, Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne 3004, Victoria, Australia 2 Regional HPV Labnet Reference Laboratory, Department of Microbiology and Infectious Diseases, The Royal Women's Hospital, Parkville 3052, Victoria, Australia 3 Murdoch Children's Research Institute, Parkville 3052, Victoria, Australia 4 School of Medicine, Faculty of Health, Deakin University, Geelong 3220, Victoria, Australia 5 Commonwealth Scientific and Industrial Research Organisation, Livestock Industries, Australian Animal Health Laboratory, Geelong 3220, Victoria, Australia 6 Department of Microbiology, Monash University, Clayton 3168, Victoria, Australia 7 Department of Infectious Diseases, Monash University, Melbourne 3004, Victoria, Australia
* Author to whom correspondence should be addressed.
Received: 27 May 2013 / Revised: 1 September 2013 / Accepted: 12 September 2013 / Published: 18 September 2013
(This article belongs to the Section Animal Viruses)
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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 (CC BY 3.0).
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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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