HIV-1 Nef mediates lymphocyte chemotaxis and activation by infected macrophages.
Infection of macrophage lineage cells is a feature of primate lentivirus replication, and several properties of primate lentiviruses seem to have evolved to promote the infection of macrophages. Here we demonstrate that the accessory gene product Nef induces the production of two CC-chemokines, macrophage inflammatory proteins 1alpha and 1beta, by HIV-1-infected macrophages. Adenovirus-mediated expression of Nef in primary macrophages was sufficient for chemokine induction. Supernatants from Nef-expressing macrophages induced both the chemotaxis and activation of resting T lymphocytes, permitting productive HIV-1 infection. These results indicate a role for Nef in lymphocyte recruitment and activation at sites of virus replication.
Swingler
S
S
University of Massachusetts Medical Center, Program in Molecular Medicine, 373 Plantation Street, Worcester, Massachusetts 01605, USA.
Mann
A
A
Jacqué
J
J
Brichacek
B
B
Sasseville
V G
VG
Williams
K
K
Lackner
A A
AA
Janoff
E N
EN
Wang
R
R
Fisher
D
D
Stevenson
M
M
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D054407:Chemokine CCL4; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D002633:Chemotaxis / Q000187:drug effects; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000096:biosynthesis; D018792:Encephalitis, Viral / Q000276:immunology / Q000821:virology; D015693:Gene Products, nef / Q000235:genetics / Q000502:physiology*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D008251:Macaca; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis / Q000235:genetics; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D009154:Mutation; D015302:Simian Immunodeficiency Virus / Q000187:drug effects / Q000254:growth & development / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D014779:Virus Replication / Q000187:drug effects; D054311:nef Gene Products, Human Immunodeficiency Virus
D054407:Chemokine CCL4; D018925:Chemokines; D017077:Culture Media, Conditioned; D016207:Cytokines; D015693:Gene Products, nef; D019402:Macrophage Inflammatory Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus