Author : Alexandre Sze
Publisher :
ISBN 13 :
Total Pages : pages
Book Rating : 4.:/5 (14 download)
Book Synopsis Molecular Mechanisms of Monocyte Depletion and CD4+ T-cell Persistence During Human T-cell Leukemia Virus Infection by : Alexandre Sze
Download or read book Molecular Mechanisms of Monocyte Depletion and CD4+ T-cell Persistence During Human T-cell Leukemia Virus Infection written by Alexandre Sze and published by . This book was released on 2018 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: "Human T-cell Leukemia Virus type 1 (HTLV-1) was the first human retrovirus discovered in 1980. It is the causal agent of two well characterized human diseases, Adult T-cell Leukemia (ATL) and HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP). Few treatment options have been developed for ATL and HAM/TSP; the median survival times for ATL remains under a year, and treatment options of HAM/TSP remain palliative in nature. Thankfully the incidence of disease in HTLV-1 infected patients is relatively low, with only approximately 5% of individuals developing ATL and 2% HAM/TSP. One major obstacle in the development of effective therapies is a lack of understanding regarding the factors that determine HTLV-1 associated pathology. The route of transmission, contaminated breast milk and blood, almost exclusively lead to ATL or HAM/TSP development respectively, but it is unclear as to why. This suggests that the early events of HTLV-1 infection may be key in discerning pathological outcomes. Unfortunately this time point is understudied, in part due to the fact that de novo infection is asymptomatic. The activity of cytotoxic T-cell lymphocytes seems to be vital in controlling viral replication, and is likely a key determinant in disease progression. We thus set out to study the early events of HTLV-1 infection in two important immunologically relevant peripheral blood mononuclear cell populations, monocytes and CD4+ T-cells. HTLV-1 infection of primary human monocytes resulted in the depletion of this cell type. This was not mediated by viral accessory proteins, as host restriction factor SAMHD1 prevented the completion of reverse transcription. The DNA by-products of this inhibition induced a potent STING-mediated immunological response, that triggered Bax and IRF3 activation and complex formation that led to apoptosis. Infection of activated CD4+ T-cells on the other hand, resulted in persistent cellular survival. This was mediated by the viral accessory protein Tax, known to have oncogenic properties. Tax expression activated the AKT pathway, which resulted in the inactivation of the pro-apoptotic FOXO3a transcription factor. This led to the long-term survival of an activated CD4+ T-cell population that was capable of viral transmission. Overall this work has demonstrated the molecular consequences of HTLV-1 infection in two important cell types, monocytes and CD4+ T-cells. These events likely shape the subsequent immunological events that control viral replication and likely influence HTLV-1 disease pathology." --
