Human Immunodeficiency Virus Type 2 Gag Interacts Specifically with PRP4, a Serine-Threonine Kinase, and Inhibits Phosphorylation of Splicing Factor SF2
| Autor: | Jane F. Allen, Erin M. Bennett, Andrew M. L. Lever |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
Ribonucleoprotein
U4-U6 Small Nuclear viruses Immunology Gene Products gag Biology Protein Serine-Threonine Kinases Microbiology Virus Cell Line Splicing factor Virology Two-Hybrid System Techniques Chlorocebus aethiops Animals Humans Phosphorylation Protein kinase A Serine/threonine-specific protein kinase Serine-Arginine Splicing Factors Kinase Nuclear Proteins RNA-Binding Proteins Molecular biology Virus-Cell Interactions Capsid Insect Science RNA splicing COS Cells HIV-2 |
| Popis: | Using a yeast two-hybrid screen of a T-cell cDNA library to identify cellular proteins that bind to the human immunodeficiency virus type 2 (HIV-2) Gag polyprotein, we identified PRP4, a serine-threonine protein kinase. Specific interaction of PRP4 and HIV-2 Gag was confirmed in in vitro and in vivo assays. The interacting region of HIV-2 Gag is located in the conserved matrix and capsid domains, while both the RS (arginine-serine-rich) domain and the KS (kinase) domain of PRP4 are able to bind to HIV-2 Gag. PRP4 is not incorporated into virus particles. HIV-2 Gag is able to inhibit PRP4-mediated phosphorylation of the splicing factor SF2. This is also observed with Gag from simian immunodeficiency virus, a closely related virus, but not with Gag from human T-cell lymphotropic virus type 1. Our results provide evidence for a novel interaction between Gag and a cellular protein kinase involved in the control of constitutive splicing in two closely related retroviruses. We hypothesize that as Gag accumulates in the cell, down regulation of splicing occurs through reduced phosphorylation of SF2. At late stages of infection, this interaction may replace the function of the early viral regulatory protein Rev. |
| Databáze: | OpenAIRE |
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