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Journal of Virology, July 2005, p. 8454-8469, Vol. 79, No. 13
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.13.8454-8469.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Virus Isolates during Acute and Chronic Human Immunodeficiency Virus Type 1 Infection Show Distinct Patterns of Sensitivity to Entry Inhibitors

Peter Rusert,1 Herbert Kuster,1 Beda Joos,1 Benjamin Misselwitz,1 Cornelia Gujer,1 Christine Leemann,1 Marek Fischer,1 Gabriela Stiegler,2 Hermann Katinger,2 William C. Olson,3 Rainer Weber,1 Leonardo Aceto,1 Huldrych F. Günthard,1 and Alexandra Trkola1*

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich Switzerland,1 Polymun Scientific, Vienna, Austria,2 Progenics Pharmaceuticals, Tarrytown, New York3

Received 26 October 2004/ Accepted 8 December 2004

We studied the effect of entry inhibitors on 58 virus isolates derived during acute and chronic infection to validate these inhibitors in vitro and to probe whether viruses at early and chronic disease stages exhibit general differences in the interaction with entry receptors. We included members of all types of inhibitors currently identified: (i) agents that block gp120 binding to CD4 (CD4-IgG2 and monoclonal antibody [MAb] IgG1b12), (ii) compounds that block the interaction with CCR5 (the chemokine RANTES/CCL5, the small-molecule inhibitor AD101, and the anti-CCR5 antibody PRO 140), (iii) the fusion inhibitor enfuvirtide (T-20), and (iv) neutralizing antibodies directed against gp120 (MAb 2G12) and gp41 (MAbs 2F5 and 4E10). No differences between viruses from acute and chronic infections in the susceptibility to inhibitors targeting the CD4 binding site, CCR5, or fusion or to MAb 2G12 were apparent, rendering treatment with entry inhibitors feasible across disease stages. The notable exceptions were antibodies 2F5 and 4E10, which were more potent in inhibiting viruses from acute infection (P = 0.0088 and 0.0005, respectively), although epitopes of these MAbs were equally well preserved in both groups. Activities of these MAbs correlated significantly with each other, suggesting that common features of the viral envelope modulate their potencies.

* Corresponding author. Mailing address: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Ramistrasse 100, 8091 Zurich, Switzerland. Phone: 41-1-255-5976. Fax: 41-1-255-3291. E-mail: alexandra.trkola{at}usz.ch.

Journal of Virology, July 2005, p. 8454-8469, Vol. 79, No. 13
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.13.8454-8469.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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