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Journal of Virology, August 2009, p. 7783-7788, Vol. 83, No. 15
0022-538X/09/$08.00+0     doi:10.1128/JVI.00673-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Cross-Subtype Neutralization Sensitivity despite Monoclonal Antibody Resistance among Early Subtype A, C, and D Envelope Variants of Human Immunodeficiency Virus Type 1{triangledown}

Catherine A. Blish,1,2 Zahra Jalalian-Lechak,1 Stephanie Rainwater,1 Minh-An Nguyen,1 Ozge C. Dogan,1 and Julie Overbaugh1*

Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. North, Seattle, Washington 98109,1 Department of Medicine, University of Washington School of Medicine, Seattle, Washington 981952

Received 1 April 2009/ Accepted 18 May 2009

The human immunodeficiency virus type 1 (HIV-1) variants that are transmitted to newly infected individuals are the primary targets of interventions, such as vaccines and microbicides, aimed at preventing new infections. Newly acquired subtype A, B, and C variants have been the focus of neutralization studies, although many of these viruses, particularly of subtypes A and B, represent viruses circulating more than a decade ago. In order to better represent the global diversity of transmitted HIV-1 variants, an additional 31 sexually transmitted Kenyan HIV-1 env genes, representing several recent infections with subtype A, as well as subtypes A/D, C, and D, were cloned, and their neutralization profiles were characterized. Most env variants were resistant to neutralization by the monoclonal antibodies (MAbs) b12, 4E10, 2F5, and 2G12, suggesting that targeting the epitopes of these MAbs may not be effective against variants that are spreading in areas of endemicity. However, significant cross-subtype neutralization by plasma was observed, indicating that there may be other epitopes, not yet defined by the limited available MAbs, which could be recognized more broadly.


* Corresponding author. Mailing address: Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. North, Mailstop C3-168, Seattle, WA 98109-1024. Phone: (206) 667-3524. Fax: (206) 667-6524. E-mail: joverbau{at}fhcrc.org

{triangledown} Published ahead of print on 27 May 2009.


Journal of Virology, August 2009, p. 7783-7788, Vol. 83, No. 15
0022-538X/09/$08.00+0     doi:10.1128/JVI.00673-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.




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