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Journal of Virology, March 2001, p. 2246-2252, Vol. 75, No. 5
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.5.2246-2252.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Reversal of Human Immunodeficiency Virus Type 1 IIIB to a Neutralization-Resistant Phenotype in an Accidentally Infected Laboratory Worker with a Progressive Clinical Course

Tim Beaumont,1,2 Ad van Nuenen,1,2 Silvia Broersen,1,2 William A. Blattner,3 Vladimir V. Lukashov,2,4 and Hanneke Schuitemaker1,2,*

Department of Clinical Viro-Immunology, CLB Sanquin, and Laboratory for Experimental and Clinical Immunology1 and Human Retrovirus Laboratory4 of the University of Amsterdam, Academic Medical Center,2 Amsterdam, The Netherlands, and Institute of Human Virology, University of Maryland, Baltimore, Maryland 212013

Received 13 September 2000/Accepted 8 December 2000

The role of humoral immunity in controlling human immunodeficiency virus type 1 (HIV-1) is still controversial. The resistance of primary HIV-1 variants to neutralization by antibodies, sera from HIV-1-infected patients, and soluble CD4 protein has been suggested to be a prerequisite for the virus to establish persistence in vivo. To further test this hypothesis, we studied the neutralization sensitivity of two IIIB/LAV variants that were isolated from a laboratory worker who accidentally was infected with the T-cell-line-adapted neutralization-sensitive IIIB isolate. Compared to the original virus in the inoculum, the reisolated viruses showed an increased resistance to neutralization over time. The ratio of nonsynonymous to synonymous nucleotide substitutions in the envelope gene pointed to strong positive selection. The emergence of neutralization-resistant HIV preceded disease development in this laboratory worker. Our results imply that the neutralization resistance of primary HIV may indeed be considered an escape mechanism from humoral immune control.

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

Journal of Virology, March 2001, p. 2246-2252, Vol. 75, No. 5
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.5.2246-2252.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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