Human T-cell lymphotrophic virus type I rex and p30 interactions govern the switch between virus latency and replication.
Human T-cell lymphotrophic virus type I Rex and p30 are both RNA binding regulatory proteins. Rex is a protein that interacts with a responsive element and stimulates nuclear export of incompletely spliced viral RNAs thereby increasing production of virus particles. In contrast, p30 is involved in the nuclear retention of the tax/rex mRNA leading to inhibition of virus expression and possible establishment of viral latency. How these two proteins, with apparent opposite functions, integrate in the viral replication cycle is unknown. Here, we demonstrate that Rex and p30 form ribonucleoprotein ternary complexes onto specific viral mRNA. Our results explain the selective nuclear retention of tax/rex but not other viral mRNAs by p30. Whereas p30 suppresses Rex expression, it did not affect Rex-mediated nuclear export of RNA containing the Rex response element. In contrast, Rex was able to counteract p30-mediated suppression of viral expression and restore cytoplasmic tax/rex mRNA and Tax protein expression. Together, our data demonstrate a complex regulatory mechanism of antagonizing post-transcriptional regulators evolved by human T-cell lymphotrophic virus type I to allow a vigilant control of viral gene expression.
Sinha-Datta
Uma
U
Department of Microbiology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Datta
Abhik
A
Ghorbel
Sofiane
S
Dodon
Madeleine Duc
MD
Nicot
Christophe
C
D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D015967:Gene Expression Regulation, Viral; D016370:Gene Products, rex / Q000235:genetics / Q000378:metabolism*; D017930:Genes, Reporter; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D047468:Immunoprecipitation; D010957:Plasmids; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D012191:Retroviridae Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017735:Virus Latency; D014779:Virus Replication
D016370:Gene Products, rex; D012333:RNA, Messenger; D012367:RNA, Viral; D012191:Retroviridae Proteins; C072814:tof protein, Human T-lymphotropic virus 1