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Journal of Virology, February 2009, p. 1649-1659, Vol. 83, No. 4
0022-538X/09/$08.00+0     doi:10.1128/JVI.02046-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The Human Immunodeficiency Virus Type 1 Envelope Spike of Primary Viruses Can Suppress Antibody Access to Variable Regions{triangledown}

Ralph Pantophlet,1* Meng Wang,1 Rowena O. Aguilar-Sino,1 and Dennis R. Burton1,2

Department of Immunology and Microbial Science,1 Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 920372

Received 28 September 2008/ Accepted 18 November 2008

The human immunodeficiency virus type 1 (HIV-1) envelope spike is a heavily glycosylated trimeric structure in which protein surfaces conserved between different HIV-1 isolates are particularly well hidden from antibody recognition. However, even variable regions on the spike tend to be less antigenic and immunogenic than one might have anticipated for external structures. Here we show that the envelope spike of primary viruses has an ability to restrict antibody recognition of variable regions. We show that access to an artificial epitope, introduced at multiple positions across the spike, is frequently limited, even though the epitope has been inserted at surface-exposed regions on the spike. Based on the data, we posit that restricted antibody access may be the result, at least in part, of a rigidification of the epitope sequence in the context of the spike and/or a highly effective flexible arrangement of the glycan shield on primary viruses. Evolution of the HIV envelope structure to incorporate extra polypeptide sequences into nominally accessible regions with limited antibody recognition may contribute to reducing the magnitude of antibody responses during infection and allow the virus to replicate unhindered by antibody pressure for longer periods.

* Corresponding author. Present address: Simon Fraser University, Faculty of Health Sciences, Blusson Hall, 8888 University Drive, Burnaby, British Columbia V5A 1S6, Canada. Phone: (778) 782-8648. Fax: (778) 782-5927. E-mail: rpantophlet{at}sfu.ca

{triangledown} Published ahead of print on 26 November 2008.

Journal of Virology, February 2009, p. 1649-1659, Vol. 83, No. 4
0022-538X/09/$08.00+0     doi:10.1128/JVI.02046-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



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