Genetic subtype-independent inhibition of human immunodeficiency virus type 1 replication by CC and CXC chemokines

Alexandra Trkola, William A. Paxton, Simon P. Monard, James A. Hoxie, Michael A. Siani, Darren A. Thompson, Lijun Wu, Charles R. Mackay, Richard Horuk, John P. Moore

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We have studied the breadth and potency of the inhibitory actions of the CC chemokines macrophage inhibitory protein 1α (MIP-1α), MIP-1β, 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 1α 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-1β, MIP-1α. Some M-tropic isolates, unexpectedly, were much more sensitive to RANTES than to MIP-1β, 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-1β, MIP-1α.

Original languageEnglish
Pages (from-to)396-404
Number of pages9
JournalJournal of Virology
Issue number1
Publication statusPublished - 1 Jan 1998
Externally publishedYes

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