Genetic subtype-independent inhibition of human immunodeficiency virus type 1 replication by CC and CXC chemokines.
We have studied the breadth and potency of the inhibitory actions of the CC chemokines macrophage inhibitory protein 1alpha (MIP-1alpha), MIP-1beta, and RANTES against macrophage-tropic (M-tropic) primary isolates of human immunodeficiency virus type 1 (HIV-1) and of the CXC chemokine stromal cell-derived factor 1alpha against T-cell-tropic (T-tropic) isolates, using mitogen-stimulated primary CD4+ T cells as targets. There was considerable interisolate variation in the sensitivity of HIV-1 to chemokine inhibition, which was especially pronounced for the CC chemokines and M-tropic strains. However, this variation was not obviously dependent on the genetic subtype (A through F) of the virus isolates. Peripheral blood mononuclear cell donor-dependent variation in chemokine inhibition potency was also observed. Among the CC chemokines, the rank order for potency (from most to least potent) was RANTES, MIP-1beta, MIP-1alpha. Some M-tropic isolates, unexpectedly, were much more sensitive to RANTES than to MIP-1beta, whereas other isolates showed sensitivities comparable to those of these two chemokines. Down-regulation of the CCR5 and CXCR4 receptors occurred in cells treated with the cognate chemokines and probably contributes to anti-HIV-1 activity. Thus, for CCR5, the rank order for down-regulation was also RANTES, MIP-1beta, MIP-1alpha.
Trkola
A
A
The Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10021, USA.
Paxton
W A
WA
Monard
S P
SP
Hoxie
J A
JA
Siani
M A
MA
Thompson
D A
DA
Wu
L
L
Mackay
C R
CR
Horuk
R
R
Moore
J P
JP
D019380:Anti-HIV Agents / Q000494:pharmacology; D001667:Binding, Competitive; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000494:pharmacology; D054377:Chemokine CXCL12; D018925:Chemokines / Q000494:pharmacology*; D019743:Chemokines, CXC; D015536:Down-Regulation; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology; D008264:Macrophages / Q000821:virology; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; C515255:CXCL12 protein, human; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054377:Chemokine CXCL12; D018925:Chemokines; D019743:Chemokines, CXC; D015699:HIV Envelope Protein gp120; D019402:Macrophage Inflammatory Proteins; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D011994:Recombinant Proteins