HIV-1 infection of T cells and macrophages are differentially modulated by virion-associated Hck: a Nef-dependent phenomenon.
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.
Centre for Biomedical Research, Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne 3004, Victoria, Australia.
Alyssa
A
Cornall
Johnson
J
Mak
Alison
A
Greenway
Gilda
G
Tachedjian
D020816:Amino Acid Motifs; D002460:Cell Line; D002478:Cells, Cultured; D015658:HIV Infections / Q000201:enzymology* / Q000235:genetics / Q000821:virology; D015497:HIV-1 / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000201:enzymology* / Q000821:virology; D011485:Protein Binding; D051572:Proto-Oncogene Proteins c-hck / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000201:enzymology* / Q000821:virology; D014779:Virus Replication; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D054311:nef Gene Products, Human Immunodeficiency Virus; C496631:HCK protein, human; D051572:Proto-Oncogene Proteins c-hck