The carboxy-terminal region of the human immunodeficiency virus type 1 protein Rev has multiple roles in mediating CRM1-related Rev functions.
The human immunodeficiency virus type 1 (HIV-1) regulatory protein, Rev, mediates the nuclear export of unspliced and singly spliced viral mRNAs by bridging viral RNA and export receptor human CRM1 (hCRM1). Ribonucleoprotein complex formation, including the oligomerization of Rev proteins on viral RNA, must occur to allow export. We show here that Rev-Rev interactions, which are a basis of complex formation, can be initiated without cellular factors and are subsequently enhanced by hCRM1-Ran-GTP. Furthermore, we reveal functions for the Rev carboxy-terminal (C-terminal) region, which is well conserved among many HIV-1 strains, and for which no function has been reported. This region is required for the efficient binding of Rev to hCRM1 and consequently for nuclear export, Rev-Rev dimerization, and full Rev transactivator activity. Consistent with these results, a HIV-1 proviral plasmid that expresses a C-terminally truncated Rev mutant protein produces smaller amounts of the p24 antigen than does a plasmid that possesses an intact rev gene. These results indicate the functional importance of the C-terminal region for full Rev activity, which leads to efficient HIV-1 replication.
Institute for Genetic Medicine, Hokkaido University, Japan.
Yoshiyuki
Y
Hakata
Masami
M
Yamada
Naoto
N
Mabuchi
Hisatoshi
H
Shida
D021581:Active Transport, Cell Nucleus; D001483:Base Sequence; D001665:Binding Sites; D003593:Cytoplasm / Q000378:metabolism; D019281:Dimerization; D015694:Gene Products, rev / Q000737:chemistry* / Q000502:physiology*; D005814:Genes, Viral; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D028884:Karyopherins / Q000502:physiology*; D010957:Plasmids / Q000235:genetics; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear; D017384:Sequence Deletion; D014162:Transfection; D014779:Virus Replication; D054321:rev Gene Products, Human Immunodeficiency Virus; D000097606:Exportin 1 Protein
D015694:Gene Products, rev; D028884:Karyopherins; D012333:RNA, Messenger; D012367:RNA, Viral; D018160:Receptors, Cytoplasmic and Nuclear; D054321:rev Gene Products, Human Immunodeficiency Virus; D000097606:Exportin 1 Protein