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Journal of Virology, August 1999, p. 6370-6379, Vol. 73, No. 8
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

The CC-Chemokine RANTES Increases the Attachment of Human Immunodeficiency Virus Type 1 to Target Cells via Glycosaminoglycans and Also Activates a Signal Transduction Pathway That Enhances Viral Infectivity

Alexandra Trkola,1,* Cynthia Gordon,1,2 Jamie Matthews,1 Elizabeth Maxwell,1 Tom Ketas,1 Lloyd Czaplewski,3 Amanda E. I. Proudfoot,4 and John P. Moore1,5

The Aaron Diamond AIDS Research Center,1 The Rockefeller University,5 and Department of Pathology, New York University School of Medicine,2 New York, New York; British Biotech Pharmaceuticals Ltd., Oxford, United Kingdom3; and Serono Pharmaceutical Research Institute, Geneva, Switzerland4

Received 2 March 1999/Accepted 28 April 1999

We have studied the mechanisms by which the CC-chemokine RANTES can enhance the infectivities of human immunodeficiency virus type 1 (HIV-1) and other enveloped viruses, when present at concentrations in excess of 500 ng/ml in vitro. Understanding the underlying mechanisms might throw light on fundamental processes of viral infection, in particular for HIV-1. Our principal findings are twofold: firstly, that oligomers of RANTES can cross-link enveloped viruses, including HIV-1, to cells via glycosaminoglycans (GAGs) present on the membranes of both virions and cells; secondly, that oligomers of RANTES interact with cell-surface GAGs to transduce a herbimycin A-sensitive signal which, over a period of several hours, renders the cells more permissive to infection by several viruses, including HIV-1. The enhancement mechanisms require that RANTES oligomerize either in solution or following binding to GAGs, since no viral infectivity enhancement is observed with a mutant form of the RANTES molecule that contains a single-amino-acid change (glutamic acid to serine at position 66) which abrogates oligomerization.

* Corresponding author. Mailing address: The Aaron Diamond AIDS Research Center, 455 First Ave., New York, NY 10021. Phone: (212) 725-0018. Fax: (212) 725-1126. E-mail: atrkola{at}adarc.org.

Journal of Virology, August 1999, p. 6370-6379, Vol. 73, No. 8
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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