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

Viruses

Alyssa Cornall²  Johnson Mak¹  Alison Greenway² 

[1] School of Medicine, Faculty of Health, Deakin University, Geelong 3220, Victoria, Australia; E-Mail:;Centre for Biomedical Research, Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne 3004, Victoria, Australia; E-Mails:

关键词: HIV-1;    Nef;    Hck;    macrophage;    T lymphocyte;    virion;    infectivity;   

DOI  :  10.3390/v5092235

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.