Critical role of hnRNP A1 in HTLV-1 replication in human transformed T lymphocytes.
BACKGROUND
In this study, we have examined the role of heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) in viral gene expression in T lymphocytes transformed by HTLV-1.


RESULTS
We have previously observed that hnRNP A1 (A1) down-modulates the post transcriptional activity of Rex protein of HTLV-1. Here, we tested whether the ectopic expression of a dominant negative mutant (NLS-A1-HA) defective in shuttling activity or knockdown of the hnRNPA1 gene using RNA interference could inhibit Rex-mediated export of viral mRNAs in HTLV-1 producing C91PL T-cells. We show that the expression of NLS-A1-HA does not modify the export of Rex-dependent viral mRNAs. Conversely, inhibiting A1 expression in C91PL cells by RNA interference provoked an increase in the Rex-dependent export of unspliced and singly spliced mRNAs. Surprisingly, we also observed a significant increase in proviral transcription and an accumulation of unspliced mRNAs, suggesting that the splicing process was affected. Finally, A1 knockdown in C91PL cells increased viral production by these cells. Thus, hnRNP A1 is implicated in the modulation of the level of HTLV-1 gene expression in T cells transformed by this human retrovirus.


CONCLUSIONS
These observations provide an insight into a new cellular control of HTLV-1 replication and suggest that hnRNP A1 is likely part of the regulatory mechanisms of the life cycle of this human retrovirus in T cells.
Kress
Elsa
E
Virologie Humaine INSERM-U412, Ecole Normale Supérieure de Lyon, IFR 128 Biosciences Lyon-Gerland, 46 allée d'ltalie 69364 Lyon Cedex 07, France. ekress@ens-lyon.fr
Baydoun
Hicham Hachem
HH
Bex
Françoise
F
Gazzolo
Louis
L
Duc Dodon
Madeleine
M
D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D017353:Gene Deletion; D015967:Gene Expression Regulation, Viral; D016370:Gene Products, rex / Q000235:genetics / Q000378:metabolism; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D015368:Human T-lymphotropic virus 1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D034622:RNA Interference; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000821:virology*; D014779:Virus Replication / Q000187:drug effects*
D016370:Gene Products, rex; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D012333:RNA, Messenger; D012367:RNA, Viral; C000619656:hnRNPA1 protein, human