Rat CRM1 is responsible for the poor activity of human T-cell leukemia virus type 1 Rex protein in rat cells.
Rat models of human T-cell leukemia virus type 1 (HTLV-1)-related diseases such as adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis have been reported. However, these models do not completely reproduce human diseases partly because HTLV-1 replicates poorly in rats. We investigated here the possible reason for this. We found that the activity of Rex in rat cells is quite low compared to that in human cells. As Rex function depends largely on the CRM1 protein, whose human type (human CRM1 [hCRM1]) directly binds to Rex and exports it from the nucleus to the cytoplasm, we assessed whether rat CRM1 (rCRM1) could act as well as hCRM1 as a cofactor for Rex activity. We first cloned a cDNA encoding rCRM1 and found that both rCRM1 and hCRM1 could bind to and export Rex protein to the cytoplasm with similar efficiencies. However, unlike hCRM1, rCRM1 could hardly support Rex function because of its poor ability in inducing the Rex-Rex interaction required for RNA export into the cytoplasm. These observations suggest that the poor ability of rCRM1 to act as a cofactor for Rex function may be responsible for the poor replication of HTLV-1 in rats.
Hakata
Y
Y
Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
Yamada
M
M
Shida
H
H
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D017931:DNA Primers; D016370:Gene Products, rex / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D028884:Karyopherins / Q000502:physiology*; D008969:Molecular Sequence Data; D011485:Protein Binding; D021381:Protein Transport; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014779:Virus Replication / Q000502:physiology; D000097606:Exportin 1 Protein
D017931:DNA Primers; D016370:Gene Products, rex; D028884:Karyopherins; D018160:Receptors, Cytoplasmic and Nuclear; D011994:Recombinant Proteins; D000097606:Exportin 1 Protein