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Splicing-dependent restriction of the HBZ gene by Tax underlies biphasic HTLV-1 infection
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Splicing-dependent restriction of the HBZ gene by Tax underlies biphasic HTLV-1 infection
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Splicing-dependent restriction of the HBZ gene by Tax underlies biphasic HTLV-1 infection
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Journal Article
Splicing-dependent restriction of the HBZ gene by Tax underlies biphasic HTLV-1 infection
2025
Overview
HTLV-1 is an oncovirus that encodes a transactivator Tax and a regulatory gene HBZ. HTLV-1 early or infectious replication depends on Tax; during HTLV-1 late infection, HBZ plays a crucial role in driving the proliferation of infected cells and maintaining viral persistence. The biphasic replication pattern of HTLV-1 dictated by Tax and HBZ represents a result of viral host adaptation, but how HTLV-1 coordinates Tax and HBZ expression to facilitate early and late infection remains elusive. Here we reveal that HBZ RNA splicing exhibits distinct patterns in Tax+ and Tax- HTLV-1 infected cells. We demonstrate that Tax interacts with the host spliceosome and inhibits HBZ splicing by competitively binding splicing factors including WDR83 and GPATCH1. As a result, Tax confers a natural constraint on HBZ, counterbalancing its anti-replication effect at HTLV-1 early infection, while unleashing HBZ to drive HTLV-1 mitotic propagation during late infection. The splicing-dependent restriction of HBZ by Tax thus represents a critical interplay central to HTLV-1 persistence.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
Basic-Leucine Zipper Transcription Factors - genetics
/ Basic-Leucine Zipper Transcription Factors - metabolism
/ Gene Expression Regulation, Viral
/ Gene Products, tax - genetics
/ Gene Products, tax - metabolism
/ Genes
/ HTLV-I Infections - genetics
/ HTLV-I Infections - metabolism
/ HTLV-I Infections - virology
/ Human T-lymphotropic virus 1 - genetics
/ Human T-lymphotropic virus 1 - physiology
/ Humans
/ Leukemia
/ Medicine and Health Sciences
/ Proteins
/ Research and analysis methods
/ Retroviridae Proteins - genetics
/ Retroviridae Proteins - metabolism
/ Viruses
