Strategies to inhibit viral protein nuclear import: HIV-1 as a target.
Nuclear import is a critical step in the life cycle of HIV-1. During the early (preintegration) stages of infection, HIV-1 has to transport its preintegration complex into the nucleus for integration into the host cell chromatin, while at the later (postintegration) stages viral regulatory proteins Tat and Rev need to get into the nucleus to stimulate transcription and regulate splicing and nuclear export of subgenomic and genomic RNAs. Given such important role of nuclear import in HIV-1 life cycle, this step presents an attractive target for antiviral therapeutic intervention. In this review, we describe the current state of our understanding of the interactions regulating nuclear import of the HIV-1 preintegration complex and describe current approaches to inhibit it. This article is part of a Special Issue entitled: Regulation of Signaling and Cellular Fate through Modulation of Nuclear Protein Import.
Levin
Aviad
A
Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Loyter
Abraham
A
Bukrinsky
Michael
M
D021581:Active Transport, Cell Nucleus / Q000187:drug effects* / Q000502:physiology; D019380:Anti-HIV Agents / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology*; D054298:Human Immunodeficiency Virus Proteins / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D019913:Nuclear Localization Signals / Q000502:physiology; D010455:Peptides / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology
D019380:Anti-HIV Agents; D054298:Human Immunodeficiency Virus Proteins; D019913:Nuclear Localization Signals; D010455:Peptides