HTLV-1: Regulating the Balance Between Proviral Latency and Reactivation
نویسندگان
چکیده
HTLV-1 plus-strand transcription begins with the production of doubly-spliced tax/rex transcripts, the levels of which are usually undetectable in freshly isolated peripheral blood mononuclear cells (PBMCs) from HTLV-1-infected individuals. However, the presence of a sustained chronically active cytotoxic T-cell response to HTLV-1 antigens in virtually all HTLV-1-infected individuals, regardless of their proviral load, argues against complete latency of the virus in vivo. There is an immediate burst of plus-strand transcription when blood from infected individuals is cultured ex vivo. How is the HTLV-1 plus strand silenced in PBMCs? Is it silenced in other anatomical compartments within the host? What reactivates the latent provirus in fresh PBMCs? While plus-strand transcription of the provirus appears to be intermittent, the minus-strand hbz transcripts are present in a majority of cells, albeit at low levels. What regulates the difference between the 5'- and 3'-LTR promoter activities and thereby the tax-hbz interplay? Finally, T lymphocytes are a migratory population of cells that encounter variable environments in different compartments of the body. Could these micro-environment changes influence the reactivation kinetics of the provirus? In this review we discuss the questions raised above, focusing on the early events leading to HTLV-1 reactivation from latency, and suggest future research directions.
منابع مشابه
Glucose Metabolism and Oxygen Availability Govern Reactivation of the Latent Human Retrovirus HTLV-1
The human retrovirus HTLV-1 causes a hematological malignancy or neuroinflammatory disease in ∼10% of infected individuals. HTLV-1 primarily infects CD4+ T lymphocytes and persists as a provirus integrated in their genome. HTLV-1 appears transcriptionally latent in freshly isolated cells; however, the chronically active anti-HTLV-1 cytotoxic T cell response observed in infected individuals indi...
متن کاملAssessment of HTLV-I proviral load, HIV viral load and CD4 T cell count in infected subjects; with an emphasis on viral replication in co-infection
Objective(s): HTLV-I and HIV virus quantification is an important marker for assessment of virus activities. Since there is a direct relationship between the number of virus and disease progression, HTLV- I and HIV co-infection might have an influence on the development of viral associated diseases, thus, viral replication of these viruses and co-infection were evaluated. Materials and...
متن کاملP178: Can Human T-Lymphotropic Virus Proviral Load Predict the Severity of Clinical Features in HAM/TSP Patients?
HTLV-1 is the causative agent for a neurologic disease named HTLV-I- associated myelopathy/tropical spastic paraparesis (HAM/TSP). Paraparesis of the lower limbs which appears gradually is the most common clinical feature of this disease. The indirect involvement of the nervous system by lymphocytes is more probable than the direct attack of the virus to the neurons. The proviral load (PVL) is ...
متن کاملEvaluation of HTLV-1 activity in HAM/TSP patients using proviral load and Tax mRNA expression after In Vitro lymphocyte activation
Objective(s):HTLV-1 is the first human retrovirus that has been recognized and is associated with HAM/TSP and ATLL. Studies have shown that less than five percent of HTLV-1 infected carriers develop HAM/TSP or ATLL and about ninety-five percent remain asymptomatic. Therefore, the proviral load with Tax may affect cellular genes such as cytokines and oncogenes, as well as involve in pathogenicit...
متن کاملGenome-wide Determinants of Proviral Targeting, Clonal Abundance and Expression in Natural HTLV-1 Infection
The regulation of proviral latency is a central problem in retrovirology. We postulate that the genomic integration site of human T lymphotropic virus type 1 (HTLV-1) determines the pattern of expression of the provirus, which in turn determines the abundance and pathogenic potential of infected T cell clones in vivo. We recently developed a high-throughput method for the genome-wide amplificat...
متن کامل