Human T-cell leukemia virus type 1 (HTLV-1) bZIP protein interacts with the cellular transcription factor CREB to inhibit HTLV-1 transcription

Autor: Isabelle Lemasson, Sabine Thébault, Benoit Barbeau, Matthew R. Lewis, Jennifer K. Nyborg, Patrick Hivin, Nicholas Polakowski, Jean-Michel Mesnard, Marie-Hélène Cavanagh
Přispěvatelé: East Carolina University [Greenville] (ECU), University of North Carolina System (UNC), Colorado State University [Fort Collins] (CSU), Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Infectiologie, CHU de Québec, Infections rétrovirales et signalisation cellulaire (IRSC), Université Montpellier 1 (UM1)-Centre National de la Recherche Scientifique (CNRS), Département des Sciences Biologiques [Montréal], Université du Québec à Montréal = University of Québec in Montréal (UQAM), ARC
Jazyk: angličtina
Rok vydání: 2007
Předmět:
Transcription
Genetic

viruses
Activating transcription factor
rétrovirus
MESH: Down-Regulation
Transactivation
MESH: Protein Structure
Tertiary

MESH: Gene Expression Regulation
Viral

0302 clinical medicine
Retrovirus
Transcription (biology)
Gene expression
MESH: Gene Products
tax

MESH: Animals
Cyclic AMP Response Element-Binding Protein
Promoter Regions
Genetic

Genetics
0303 health sciences
Human T-lymphotropic virus 1
biology
bZIP domain
Gene Products
tax

3. Good health
Cell biology
Genome Replication and Regulation of Viral Gene Expression
MESH: Promoter Regions (Genetics)
Basic-Leucine Zipper Transcription Factors
[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology
MESH: Cyclic AMP Response Element-Binding Protein
Gene Expression Regulation
Viral

Immunology
Down-Regulation
[SDV.CAN]Life Sciences [q-bio]/Cancer
MESH: Basic-Leucine Zipper Transcription Factors
CREB
Microbiology
Cell Line
ATF/CREB
03 medical and health sciences
Viral Proteins
Virology
Animals
Humans
leucémie
030304 developmental biology
MESH: Human T-lymphotropic virus 1
MESH: Humans
MESH: Transcription
Genetic

biology.organism_classification
MESH: Viral Proteins
Protein Structure
Tertiary

MESH: Cell Line
HTLV-1
Insect Science
biology.protein
030215 immunology
Zdroj: Journal of Virology
Journal of Virology, American Society for Microbiology, 2007, 81 (4), pp.1543-53. ⟨10.1128/JVI.00480-06⟩
ISSN: 0022-538X
1098-5514
DOI: 10.1128/JVI.00480-06⟩
Popis: The complex human T-cell leukemia virus type 1 (HTLV-1) retrovirus encodes several proteins that are unique to the virus within its 3′-end region. Among them, the viral transactivator Tax and posttranscriptional regulator Rex are well characterized, and both positively regulate HTLV-1 viral expression. Less is known about the other regulatory proteins encoded in this region of the provirus, including the recently discovered HBZ protein. HBZ has been shown to negatively regulate basal and Tax-dependent HTLV-1 transcription through its ability to interact with specific basic-leucine zipper (bZIP) proteins. In the present study, we found that HBZ reduces HTLV-1 transcription and virion production. We then characterized the interaction between HBZ and the cellular transcription factor CREB. CREB plays a critical role in Tax-mediated HTLV-1 transcription by forming a complex with Tax that binds to viral cyclic AMP-response elements (CREs) located within the viral promoter. We found that HBZ and CREB interact in vivo and directly in vitro, and this interaction occurs through the bZIP domain of each protein. We also found that CREM-Ia and ATF-1, which share significant homology in their bZIP domains with the bZIP domain of CREB, interact with HBZ-bZIP. The interaction between CREB and HBZ prevents CREB binding to the viral CRE elements in vitro and in vivo, suggesting that the reduction in HTLV-1 transcription by HBZ is partly due to the loss of CREB at the promoter. We also found that HBZ displaces CREB from a cellular CRE, suggesting that HBZ may deregulate CREB-dependent cellular gene expression.
Databáze: OpenAIRE