Disrupting surfaces of Nef required for downregulation of CD4 and for enhancement of virion infectivity attenuates simian immunodeficiency virus replication in vivo

Iafrate, A. J., Carl, S., Bronson, S., Stahl-Hennig, C., Swigut, T., Skowronski, J., Kirchhoff, F. (November 2000) Disrupting surfaces of Nef required for downregulation of CD4 and for enhancement of virion infectivity attenuates simian immunodeficiency virus replication in vivo. Journal of Virology, 74 (21). pp. 9836-9844. ISSN 0022-538X

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URL: http://www.ncbi.nlm.nih.gov/pubmed/11024110
DOI: 10.1128/JVI.74.21.9836-9844.2000

Abstract

The multifunctional simian and human immunodeficiency virus (SIV and HIV) Nef proteins are important for virulence. We studied the importance of selected Nef functions using an SIV Nef with mutations in two regions that are required for CD4 downregulation. This Nef mutant is defective for downregulating CD4 and, in addition, for enhancing SN infectivity and induction of SIV replication from infected quiescent peripheral blood mononuclear cells, but not for other known functions, including downregulation of class I major histocompatibility complex (MHC) cell surface expression. Replication of SIV containing this Nef variant in rhesus monkeys was attenuated early during infection. Subsequent increases in viral load coincided with selection of reversions and second-site compensatory changes in Nef. Our results indicate that the surfaces of Nef that mediate CD4 downregulation and the enhancement of virion infectivity are critical for SIV replication in vivo. Furthermore, these findings indicate that class I MHC downregulation by Nef is not sufficient for SIV virulence early in infection.

Item Type: Paper
Uncontrolled Keywords: LONG-TERM SURVIVOR T-CELL ACTIVATION HIV-1 NEF RHESUS MACAQUES DOWN-REGULATION TRANSGENIC MICE SIV NEF TYPE-1 PROTEIN GENE
Subjects: diseases & disorders > viral diseases > HIV
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
diseases & disorders > viral diseases
CSHL Authors:
Communities: CSHL labs > Skowronski lab
Depositing User: Matt Covey
Date: November 2000
Date Deposited: 31 Jan 2014 15:22
Last Modified: 31 Jan 2014 15:22
PMCID: PMC102020
Related URLs:
URI: http://repository.cshl.edu/id/eprint/29375

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