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Journal of Virology, April 2001, p. 3657-3665, Vol. 75, No. 8
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.8.3657-3665.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Modulation of Different Human Immunodeficiency Virus Type 1 Nef Functions during Progression to AIDS

Silke Carl,1 Thomas C. Greenough,2 Mandy Krumbiegel,1 Michael Greenberg,3 Jacek Skowronski,3 John L. Sullivan,2 and Frank Kirchhoff1,*

Institute for Clinical and Molecular Virology, Friedrich-Alexander University, D-91054 Erlangen, Germany1; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 016052; and Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 117243

Received 7 November 2000/Accepted 17 January 2001

The human immunodeficiency virus type 1 (HIV-1) Nef protein has several independent functions that might contribute to efficient viral replication in vivo. Since HIV-1 adapts rapidly to its host environment, we investigated if different Nef properties are associated with disease progression. Functional analysis revealed that nef alleles obtained during late stages of infection did not efficiently downmodulate class I major histocompatibility complex but were highly active in the stimulation of viral replication. In comparison, functional activity in downregulation of CD4 and enhancement of HIV-1 infectivity were maintained or enhanced after AIDS progression. Our results demonstrate that various Nef activities are modulated during the course of HIV-1 infection to maintain high viral loads at different stages of disease progression. These findings suggest that all in vitro Nef functions investigated contribute to AIDS pathogenesis and indicate that nef variants with increased pathogenicity emerge in a significant number of HIV-1-infected individuals.

* Corresponding author. Present address: Abteilung Virologie, Institut fur Mikrobiologie und Immunologie, Universitatsklinikum Ulm, 89081 Ulm, Germany. Phone: 49-731-502-3344. Fax: 49-731-502-3337.frank.kirchhoff{at}medizin.uni-ulm.de.

Journal of Virology, April 2001, p. 3657-3665, Vol. 75, No. 8
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.8.3657-3665.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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