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Journal of Virology, January 1999, p. 684-694, Vol. 73, No. 1
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Enhancement of Human Immunodeficiency Virus Type 1 Infection by the CC-Chemokine RANTES Is Independent of the Mechanism of Virus-Cell Fusion

Cynthia J. Gordon,1,2 Mark A. Muesing,1,3 Amanda E. I. Proudfoot,4 Christine A. Power,4 John P. Moore,1,3 and Alexandra Trkola1,3,*

The Aaron Diamond AIDS Research Center,1 Department of Pathology, New York University School of Medicine,2 and The Rockefeller University,3 New York, New York, and Serono Pharmaceutical Research Institute, Geneva, Switzerland4

Received 13 August 1998/Accepted 9 October 1998

We have studied the effects of CC-chemokines on human immunodeficiency virus type 1 (HIV-1) infection, focusing on the infectivity enhancement caused by RANTES. High RANTES concentrations increase the infectivity of HIV-1 isolates that use CXC-chemokine receptor 4 for entry. However, RANTES can have a similar enhancing effect on macrophagetropic viruses that enter via CC-chemokine receptor 5 (CCR5), despite binding to the same receptor as the virus. Furthermore, RANTES enhances the infectivity of HIV-1 pseudotyped with the envelope glycoprotein of murine leukemia virus or vesicular stomatitis virus, showing that the mechanism of enhancement is independent of the route of virus-cell fusion. The enhancing effects of RANTES are not mediated via CCR5 or other known chemokine receptors and are not mimicked by MIP-1alpha or MIP-1beta . The N-terminally modified derivative aminooxypentane RANTES (AOP-RANTES) efficiently inhibits HIV-1 infection via CCR5 but otherwise mimics RANTES by enhancing viral infectivity. There are two mechanisms of enhancement: one apparent when target cells are pretreated with RANTES (or AOP-RANTES) for several hours, and the other apparent when RANTES (or AOP-RANTES) is added during virus-cell absorption. We believe that the first mechanism is related to cellular activation by RANTES, whereas the second is an increase in virion attachment to target cells.

* 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, January 1999, p. 684-694, Vol. 73, No. 1
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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