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Journal of Virology, September 2000, p. 7699-7707, Vol. 74, No. 17
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Increased Neutralization Sensitivity and Reduced Replicative Capacity of Human Immunodeficiency Virus Type 1 after Short-Term In Vivo or In Vitro Passage through Chimpanzees

Tim Beaumont,1,2 Silvia Broersen,1,2 Ad van Nuenen,1,2 Han G. Huisman,2,3 Ana-Maria de Roda Husman,1,2,dagger Jonathan L. Heeney,4 and Hanneke Schuitemaker1,2,*

Department of Clinical Viro-Immunology1 and Department of Pathophysiology of Plasma Proteins,3 CLB, and Laboratory for Experimental and Clinical Immunology, University of Amsterdam, Academic Medical Center,2 Amsterdam, and Department of Virology, Biomedical Primate Research Centre, Rijswijk,4 The Netherlands

Received 10 November 1999/Accepted 19 May 2000

Development of disease is extremely rare in chimpanzees when inoculated with either T-cell-line-adapted neutralization-sensitive or primary human immunodeficiency virus type 1 (HIV-1), at first excluding a role for HIV-1 neutralization sensitivity in the clinical course of infection. Interestingly, we observed that short-term in vivo and in vitro passage of primary HIV-1 isolates through chimpanzee peripheral blood mononuclear cells (PBMC) resulted in a neutralization-sensitive phenotype. Furthermore, an HIV-1 variant reisolated from a chimpanzee 10 years after experimental infection was still sensitive to neutralization by soluble CD4, the CD4 binding site recognizing antibody IgG1b12 and autologous chimpanzee serum samples, but had become relatively resistant to neutralization by polyclonal human sera and neutralizing monoclonal antibodies. The initial adaptation of HIV-1 to replicate in chimpanzee PBMC seemed to coincide with a selection for viruses with low replicative kinetics. Neither coreceptor usage nor the expression level of CD4, CCR5, or CXCR4 on chimpanzee PBMC compared to human cells could explain the phenotypic changes observed in these chimpanzee-passaged viruses. Our data suggest that the increased neutralization sensitivity of HIV-1 after replication in chimpanzee cells may in part contribute to the long-term asymptomatic HIV-1 infection in experimentally infected chimpanzees.

* Corresponding author. Mailing address: Department of Clinical Viro-Immunology, CLB, Plesmanlaan 125, 1066 CX Amsterdam, The Netherlands. Phone: 31-20-5123317. Fax: 31-20-5123310. E-mail: J_Schuitemaker{at}CLB.nl.

dagger Present address: Department of Microbiological Laboratory for Healthcare, RIVM, Bilthoven, The Netherlands.

Journal of Virology, September 2000, p. 7699-7707, Vol. 74, No. 17
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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