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HIV-1 Infection of T Cells and Macrophages Are Differentially Modulated by Virion-Associated Hck: A Nef-Dependent Phenomenon
Centre for Biomedical Research, Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne 3004, Victoria, Australia
Regional HPV Labnet Reference Laboratory, Department of Microbiology and Infectious Diseases, The Royal Women's Hospital, Parkville 3052, Victoria, Australia
Murdoch Children's Research Institute, Parkville 3052, Victoria, Australia
School of Medicine, Faculty of Health, Deakin University, Geelong 3220, Victoria, Australia
Commonwealth Scientific and Industrial Research Organisation, Livestock Industries, Australian Animal Health Laboratory, Geelong 3220, Victoria, Australia
Department of Microbiology, Monash University, Clayton 3168, Victoria, Australia
Department of Infectious Diseases, Monash University, Melbourne 3004, Victoria, Australia
* Author to whom correspondence should be addressed.
Received: 27 May 2013; in revised form: 1 September 2013 / Accepted: 12 September 2013 / Published: 18 September 2013
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
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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.
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(9):2235-2252.
Cornall, Alyssa; Mak, Johnson; Greenway, Alison; Tachedjian, Gilda. 2013. "HIV-1 Infection of T Cells and Macrophages Are Differentially Modulated by Virion-Associated Hck: A Nef-Dependent Phenomenon." Viruses 5, no. 9: 2235-2252.