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

doi:10.1128/JVI.75.8.3657-3665.2001

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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 efficientviral replication in vivo. Since HIV-1 adapts rapidly to its hostenvironment, we investigated if different Nef properties are associatedwith disease progression. Functional analysis revealed that nefalleles obtained during late stages of infection did not efficientlydownmodulate class I major histocompatibility complex but werehighly active in the stimulation of viral replication. In comparison,functional activity in downregulation of CD4 and enhancement ofHIV-1 infectivity were maintained or enhanced after AIDS progression.Our results demonstrate that various Nef activities are modulatedduring the course of HIV-1 infection to maintain high viral loadsat different stages of disease progression. These findings suggestthat all in vitro Nef functions investigated contribute to AIDSpathogenesis and indicate that nef variants with increased pathogenicityemerge in a significant number of HIV-1-infectedindividuals.

^* Corresponding author. Present address: Abteilung Virologie, Institut fur Mikrobiologie und Immunologie, UniversitatsklinikumUlm, 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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