Identification of a heterogeneous nuclear ribonucleoprotein-recognition region in the HIV Rev protein.
The Rev protein is a key regulator of human immunodeficiency virus type 1 (HIV-1) gene expression. Rev is primarily known as an adaptor protein for nuclear export of HIV RNAs. However, Rev also contributes to numerous other processes by less well known mechanisms. Understanding the functional nature of Rev requires extensive knowledge of its cellular interaction partners. Here we demonstrate that Rev interacts with members of a large family of multifunctional host cell factors called hnRNPs. Rev employs amino acids 9-14 for specific binding to the heterogeneous nuclear ribonucleoproteins (hnRNP) A1, Q, K, R, and U. In addition, Rev interacts with hnRNP E1 and E2 by a different mechanism. The set of hnRNPs recognized by the N terminus of Rev feature RGG boxes. Exemplary testing of hnRNP A1 revealed a critical role of arginine residues within the RGG box for interaction with Rev. Finally, we demonstrate that expression levels of hnRNP A1, Q, K, R, and U influence HIV-1 production by persistently infected astrocytes, linking these hnRNPs to HIV replication. The novel interaction of HIV-1 Rev with functionally diverse hnRNPs lends further support to the idea that Rev is a multifunctional protein and may be involved in coupling HIV replication to diverse cellular processes and promoting virus-host cell interactions.
Hadian
Kamyar
K
Institute of Virology, Helmholtz Zentrum München, Research Center for Environmental Health, Ingolstaedter Landstrasse 1, D-85764 Neuherberg, Germany.
Vincendeau
Michelle
M
Mäusbacher
Nina
N
Nagel
Daniel
D
Hauck
Stefanie M
SM
Ueffing
Marius
M
Loyter
Abraham
A
Werner
Thomas
T
Wolff
Horst
H
Brack-Werner
Ruth
R
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000235:genetics / Q000378:metabolism*; D001120:Arginine / Q000235:genetics / Q000378:metabolism; D001254:Astrocytoma / Q000378:metabolism / Q000473:pathology / Q000821:virology; D001665:Binding Sites; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002846:Chromatography, Affinity; D004268:DNA-Binding Proteins; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000235:genetics / Q000378:metabolism; D034641:Heterogeneous-Nuclear Ribonucleoprotein K / Q000235:genetics / Q000378:metabolism; D034722:Heterogeneous-Nuclear Ribonucleoprotein U / Q000235:genetics / Q000378:metabolism; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D016601:RNA-Binding Proteins; D014779:Virus Replication; D054321:rev Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
D000596:Amino Acids; D004268:DNA-Binding Proteins; C439930:HNRNPR protein, human; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D034722:Heterogeneous-Nuclear Ribonucleoprotein U; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D008164:Luminescent Proteins; C094604:PCBP1 protein, human; D016601:RNA-Binding Proteins; D054321:rev Gene Products, Human Immunodeficiency Virus; D001120:Arginine