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Journal of Virology, December 1999, p. 10199-10207, Vol. 73, No. 12
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Characterization of Primary Isolate-Like Variants of Simian-Human Immunodeficiency Virus

John M. Crawford,1 Patricia L. Earl,2 Bernard Moss,2 Keith A. Reimann,3 Michael S. Wyand,4 Kelledy H. Manson,4 Miroslawa Bilska,1 Jin Tao Zhou,1 C. David Pauza,5 Paul W. H. I. Parren,6 Dennis R. Burton,6 Joseph G. Sodroski,7 Norman L. Letvin,3 and David C. Montefiori1,*

Department of Surgery, Duke University Medical Center, Durham, North Carolina 277101; Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 208922; Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center,3 and Dana-Farber Cancer Institute,7 Harvard Medical School, Boston, Massachusetts 02215; Primedica Corporation, Worcester, Massachusetts 016084; Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin 537065; and Departments of Immunology and Molecular Biology, The Scripps Research Institute, La Jolla, California 920376

Received 2 April 1999/Accepted 23 August 1999

Several different strains of simian-human immunodeficiency virus (SHIV) that contain the envelope glycoproteins of either T-cell-line-adapted (TCLA) strains or primary isolates of human immunodeficiency virus type 1 (HIV-1) are now available. One of the advantages of these chimeric viruses is their application to studies of HIV-1-specific neutralizing antibodies in preclinical AIDS vaccine studies in nonhuman primates. In this regard, an important consideration is the spectrum of antigenic properties exhibited by the different envelope glycoproteins used for SHIV construction. The antigenic properties of six SHIV variants were characterized here in neutralization assays with recombinant soluble CD4 (rsCD4), monoclonal antibodies, and serum samples from SHIV-infected macaques and HIV-1-infected individuals. Neutralization of SHIV variants HXBc2, KU2, 89.6, and 89.6P by autologous and heterologous sera from SHIV-infected macaques was restricted to an extent that these viruses may be considered heterologous to one another in their major neutralization determinants. Little or no variation was seen in the neutralization determinants on SHIV variants 89.6P, 89.6PD, and SHIV-KB9. Neutralization of SHIV HXBc2 by sera from HXBc2-infected macaques could be blocked with autologous V3-loop peptide; this was less true in the case of SHIV 89.6 and sera from SHIV 89.6-infected macaques. The poorly immunogenic but highly conserved epitope for monoclonal antibody IgG1b12 was a target for neutralization on SHIV variants HXBc2, KU2, and 89.6 but not on 89.6P and KB9. The 2G12 epitope was a target for neutralization on all five SHIV variants. SHIV variants KU2, 89.6, 89.6P, 89.6PD, and KB9 exhibited antigenic properties characteristic of primary isolates by being relatively insensitive to neutralization in peripheral blood mononuclear cells with serum samples from HIV-1-infected individuals and 12-fold to 38-fold less sensitive to inhibition with recombinant soluble CD4 than TCLA strains of HIV-1. The utility of nonhuman primate models in AIDS vaccine development is strengthened by the availability of SHIV variants that are heterologous in their neutralization determinants and exhibit antigenic properties shared with primary isolates.

* Corresponding author. Mailing address: Department of Surgery, Box 2926, Duke University Medical Center, Durham, NC 27710. Phone: (919) 684-5278. Fax: (919) 684-4288. E-mail: monte005{at}mc.duke.edu.

Journal of Virology, December 1999, p. 10199-10207, Vol. 73, No. 12
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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