In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 19, No. 2 ( 2023-2-24), p. e1011202-
Abstract:
The complex retrovirus, human T-cell leukemia virus type 1 (HTLV-1), primarily infects CD4 + T-cells in vivo . Infectious spread within this cell population requires direct contact between virally-infected and target cells. The HTLV-1 accessory protein, HBZ, was recently shown to enhance HTLV-1 infection by activating intracellular adhesion molecule 1 (ICAM-1) expression, which promotes binding of infected cells to target cells and facilitates formation of a virological synapse. In this study we show that HBZ additionally enhances HTLV-1 infection by activating expression of myoferlin (MyoF), which functions in membrane fusion and repair and vesicle transport. Results from ChIP assays and quantitative reverse transcriptase PCR indicate that HBZ forms a complex with c-Jun or JunB at two enhancer sites within the MYOF gene and activates transcription through recruitment of the coactivator p300/CBP. In HTLV-1-infected T-cells, specific inhibition of MyoF using the drug, WJ460, or shRNA-mediated knockdown of MyoF reduced infection efficiency. This effect was associated with a decrease in cell adhesion and an intracellular reduction in the abundance of HTLV-1 envelope (Env) surface unit (SU) and transmembrane domain (TM). Lysosomal protease inhibitors partially restored SU levels in WJ460-treated cells, and SU localization to LAMP-2 sites was increased by MyoF knockdown, suggesting that MyoF restricts SU trafficking to lysosomes for degradation. Consistent with these effects, less SU was associated with cell-free virus particles. Together, these data suggest that MyoF contributes to HTLV-1 infection through modulation of Env trafficking and cell adhesion.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1011202
DOI:
10.1371/journal.ppat.1011202.g001
DOI:
10.1371/journal.ppat.1011202.g002
DOI:
10.1371/journal.ppat.1011202.g003
DOI:
10.1371/journal.ppat.1011202.g004
DOI:
10.1371/journal.ppat.1011202.g005
DOI:
10.1371/journal.ppat.1011202.g006
DOI:
10.1371/journal.ppat.1011202.g007
DOI:
10.1371/journal.ppat.1011202.g008
DOI:
10.1371/journal.ppat.1011202.g009
DOI:
10.1371/journal.ppat.1011202.g010
DOI:
10.1371/journal.ppat.1011202.s001
DOI:
10.1371/journal.ppat.1011202.s002
DOI:
10.1371/journal.ppat.1011202.s003
DOI:
10.1371/journal.ppat.1011202.s004
DOI:
10.1371/journal.ppat.1011202.s005
DOI:
10.1371/journal.ppat.1011202.s006
DOI:
10.1371/journal.ppat.1011202.s007
DOI:
10.1371/journal.ppat.1011202.s008
DOI:
10.1371/journal.ppat.1011202.r001
DOI:
10.1371/journal.ppat.1011202.r002
DOI:
10.1371/journal.ppat.1011202.r003
DOI:
10.1371/journal.ppat.1011202.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2205412-1
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