Human T-cell leukemia virus type I p30 nuclear/nucleolar retention is mediated through interactions with RNA and a constituent of the 60 S ribosomal subunit.
Human T-cell leukemia virus type I is the etiological agent of adult T-cell leukemia/lymphoma, an aggressive and fatal lymphoproliferative malignancy. The virus has evolved strategies to escape immune clearance by remaining latent in most infected cells in vivo. We demonstrated previously that virally encoded p30 protein is a potent post-transcriptional inhibitor of virus replication (Nicot, C., Dundr, M., Johnson, J. M., Fullen, J. R., Alonzo, N., Fukumoto, R., Princler, G. L., Derse, D., Misteli, T., and Franchini, G. (2004) Nat. Med. 10, 197-201). p30 is unable to shuttle out of the nucleus in heterokaryon assays, suggesting the existence of specific retention signals. Because suppression of virus replication relies on nuclear retention of the tax/rex mRNA by p30, determining the retention features of p30 will offer hints to break latency in infected cells and insights into new therapeutic approaches. In this study, we used live cell imaging technologies to study the kinetics of p30 and to delineate its retention signals and their function in virus replication. Notably, this is the first study to identify p30 nucleolar retention domains. Using mutants of p30 that localized in different cellular compartments, we show that post-transcriptional control of virus replication by p30 occurs in the nucleoplasm. We further demonstrate that p30 nuclear/nucleolar retention is dependent upon de novo RNA transcripts and interactions with components of the ribosomal machinery.
Ghorbel
Sofiane
S
Department of Microbiology, Molecular Genetics, and Immunology, University of Kansas Medical Center, Kansas City, Kansas 66160-7420, USA.
Sinha-Datta
Uma
U
Dundr
Miroslav
M
Brown
Megan
M
Franchini
Genoveffa
G
Nicot
Christophe
C
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002466:Cell Nucleolus / Q000821:virology*; D002467:Cell Nucleus / Q000821:virology*; D002522:Chlorocebus aethiops; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism*; D007700:Kinetics; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D012313:RNA / Q000737:chemistry*; D012270:Ribosomes / Q000737:chemistry* / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000378:metabolism / Q000502:physiology*; D014779:Virus Replication
D017361:Viral Nonstructural Proteins; D012313:RNA