HTLV-1: Regulating the Balance Between Proviral Latency and Reactivation
File(s)
Published version
Author(s)
Kulkarni, Anurag
Bangham, Charles RM
Type
Journal Article
Abstract
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.
Date Issued
2018-03-19
Date Acceptance
2018-02-27
Citation
FRONTIERS IN MICROBIOLOGY, 2018, 9
ISSN
1664-302X
Publisher
FRONTIERS MEDIA SA
Journal / Book Title
FRONTIERS IN MICROBIOLOGY
Volume
9
Copyright Statement
© 2018 Kulkarni and Bangham. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY https://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Sponsor
Medical Research Council (MRC)
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000427717600001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
MR/K019090/1
Subjects
Science & Technology
Life Sciences & Biomedicine
Microbiology
HTLV-1
latency
virus
metabolism
hypoxia
glucose
epigenetic regulation
transcription
T-CELL LEUKEMIA
VIRUS TYPE-I
OPEN READING FRAMES
ZIPPER FACTOR HBZ
TYPE-1 HTLV-1
TAX PROTEIN
TRANSCRIPTIONAL ACTIVATION
SPASTIC PARAPARESIS
VIRAL TRANSCRIPTION
RETROVIRUS HTLV-1
Publication Status
Published
Article Number
ARTN 449