Evidence for an activation domain at the amino terminus of simian immunodeficiency virus Vpx
Gramberg T, Sunseri N, Landau NR (2010)
Publication Type: Journal article
Publication year: 2010
Journal
Book Volume: 84
Pages Range: 1387-1396
Journal Issue: 3
DOI: 10.1128/JVI.01437-09
Abstract
Vpx and Vpr are related lentiviral accessory proteins that enhance virus replication in macrophages and dendritic cells. Both proteins are packaged into virions and mediate their effects in the target cell through an interaction with an E3 ubiquitin ligase that contains DCAF1 and DDB1. When introduced into primary macrophages and dendritic cells in viruslike particles, Vpx can enhance the efficiency of a subsequent infection. Here, we confirm the ability of Vpx to enhance simian immunodeficiency virus (SIV) and human immunode-ficiency virus type 1 (HIV-1) infection of macrophages up to 100-fold by using single-cycle reporter viruses and by pretreatment of the cells with Vpx-containing viruslike particles. Vpx was also active in differentiated THP-1 cells but not in other cell lines. Induction of an antiviral state in macrophages with type I interferon significantly magnified the effect of Vpx on HIV-1 infection, suggesting that Vpx helps the virus to overcome an inducible intracellular restriction. Quantitative PCR quantitation of SIV and HIV-1 reverse transcripts in newly infected macrophages showed that the block was at an early step in reverse transcription. In spite of its structural similarity, Vpr was inactive. This difference allowed us to map the functional domains of Vpx with a panel of Vpr/Vpx chimeras. Analysis of the chimeras demonstrated that the amino-terminal domain of Vpx is important for the enhancement of infection. Fine mapping of the region indicated that amino acids at positions 9, 12, and 15 to 17 were required. Although the mutants failed to enhance infection, they retained their ability to interact with DCAF1. These findings suggest that the Vpx amino terminus contains an activation domain that serves as the binding site for a cellular restriction factor. Copyright © 2010, American Society for Microbiology. All Rights Reserved.
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APA:
Gramberg, T., Sunseri, N., & Landau, N.R. (2010). Evidence for an activation domain at the amino terminus of simian immunodeficiency virus Vpx. Journal of Virology, 84(3), 1387-1396. https://doi.org/10.1128/JVI.01437-09
MLA:
Gramberg, Thomas, Nicole Sunseri, and Nathaniel R. Landau. "Evidence for an activation domain at the amino terminus of simian immunodeficiency virus Vpx." Journal of Virology 84.3 (2010): 1387-1396.
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