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Journal of Virology, May 2001, p. 4402-4406, Vol. 75, No. 9
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.9.4402-4406.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

The LD78beta Isoform of MIP-1alpha Is the Most Potent CC-Chemokine in Inhibiting CCR5-Dependent Human Immunodeficiency Virus Type 1 Replication in Human Macrophages

Stefano Aquaro,1,* Patricia Menten,2 Sofie Struyf,2 Paul Proost,2 Jo Van Damme,2 Erik De Clercq,1 and Dominique Schols1

Laboratory of Experimental Chemotherapy1 and Laboratory of Molecular Immunology,2 Department of Microbiology and Immunology, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium

Received 14 September 2000/Accepted 29 January 2001

The CC-chemokines RANTES, macrophage inflammatory protein 1alpha (MIP-1alpha ), and MIP-1beta are natural ligands for the CC-chemokine receptor CCR5. MIP-1alpha , also known as LD78alpha , has an isoform, LD78beta , which was identified as the product of a nonallelic gene. The two isoforms differ in only 3 amino acids. LD78beta was recently reported to be a much more potent CCR5 agonist than LD78alpha and RANTES in inducing intracellular Ca2+ signaling and chemotaxis. CCR5 is expressed by human monocytes/macrophages (M/M) and represents an important coreceptor for macrophage-tropic, CCR5-using (R5) human immunodeficiency virus type 1 (HIV-1) strains to infect the cells. We compared the antiviral activities of LD78beta and the other CC-chemokines in M/M. LD78beta at 100 ng/ml almost completely blocked HIV-1 replication, while at the same concentration LD78alpha had only weak antiviral activity. Moreover, when HIV-1 infection in M/M was monitored by a flow cytometric analysis using p24 antigen intracellular staining, LD78beta proved to be the most antivirally active of the chemokines. RANTES, once described as the most potent chemokine in inhibiting R5 HIV-1 infection, was found to be considerably less active than LD78beta . LD78beta strongly downregulated CCR5 expression in M/M, thereby explaining its potent antiviral activity.

* Corresponding author. Mailing address: Department of Experimental Medicine, University of Rome "Tor Vergata," Rome, Italy. Phone: 39 06 7259 6553. Fax: 39 06 72596552. E-mail: aquaro{at}uniroma2.it.

Journal of Virology, May 2001, p. 4402-4406, Vol. 75, No. 9
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.9.4402-4406.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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