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J Virol, March 1998, p. 1876-1885, Vol. 72, No. 3
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Neutralization Sensitivity of Human Immunodeficiency Virus Type 1 Primary Isolates to Antibodies and CD4-Based Reagents Is Independent of Coreceptor Usage

Alexandra Trkola,1 Tom Ketas,1 Vineet N. KewalRamani,2 Fred Endorf,1 James M. Binley,1 Hermann Katinger,3 Jim Robinson,4 Dan R. Littman,2,5 and John P. Moore1,*

Aaron Diamond AIDS Research Center, The Rockefeller University,1 and The Skirball Institute of BioMolecular Medicine, New York University School of Medicine,2 Howard Hughes Medical Institute,5 New York, New York 10016; Institute of Applied Microbiology, University of Agriculture, Vienna, Austria3; and Department of Pediatrics, Tulane University Medical Center, New Orleans, Louisiana 701124

Received 15 September 1997/Accepted 4 December 1997

We have investigated whether the identity of the coreceptor (CCR5, CXCR4, or both) used by primary human immunodeficiency virus type 1 (HIV-1) isolates to enter CD4+ cells influences the sensitivity of these isolates to neutralization by monoclonal antibodies and CD4-based agents. Coreceptor usage was not an important determinant of neutralization titer for primary isolates in peripheral blood mononuclear cells. We also studied whether dualtropic primary isolates (able to use both CCR5 and CXCR4) were differentially sensitive to neutralization by the same antibodies when entering U87MG-CD4 cells stably expressing either CCR5 or CXCR4. Again, we found that the coreceptor used by a virus did not greatly affect its neutralization sensitivity. Similar results were obtained for CCR5- or CXCR4-expressing HOS cell lines engineered to express green fluorescent protein as a reporter of HIV-1 entry. Neutralizing antibodies are therefore unlikely to be the major selection pressure which drives the phenotypic evolution (change in coreceptor usage) of HIV-1 that can occur in vivo. In addition, the increase in neutralization sensitivity found when primary isolates adapt to growth in transformed cell lines in vitro has little to do with alterations in coreceptor usage.

* Corresponding author. Mailing address: The Aaron Diamond AIDS Research Center, 455 1st Ave., 7th floor, New York, NY 10016. Phone: (212) 725-0018. Fax: (212) 725-1126. E-mail: jmoore{at}adarc.org.




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