HIV protease cleaves the antiviral m6A reader protein YTHDF3 in the viral particle.
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
08
08
2019
accepted:
03
01
2020
revised:
26
02
2020
pubmed:
14
2
2020
medline:
6
6
2020
entrez:
14
2
2020
Statut:
epublish
Résumé
N6-methyladenosine (m6A) is the most abundant HIV RNA modification but the interplay between the m6A reader protein YTHDF3 and HIV replication is not well understood. We found that knockout of YTHDF3 in human CD4+ T-cells increases infection supporting the role of YTHDF3 as a restriction factor. Overexpression of the YTHDF3 protein in the producer cells reduces the infectivity of the newly produced viruses. YTHDF3 proteins are incorporated into HIV particles in a nucleocapsid-dependent manner permitting the m6A reader protein to limit infection in the new target cell at the step of reverse transcription. Importantly, HIV protease cleaves the virion-incorporated full-length YTHDF3 protein, a process which is blocked by HIV protease inhibitors used to treat HIV infected patients. Mass-spectrometry confirmed the proteolytic processing of YTHDF3 in the virion. Thus, HIV protease cleaves the virion-encapsidated host m6A effector protein in addition to the viral polyproteins to ensure optimal infectivity of the mature virion.
Identifiants
pubmed: 32053707
doi: 10.1371/journal.ppat.1008305
pii: PPATHOGENS-D-19-01452
pmc: PMC7043784
doi:
Substances chimiques
Antiviral Agents
0
RNA-Binding Proteins
0
YTHDF3 protein, human
0
N-methyladenosine
CLE6G00625
HIV Protease
EC 3.4.23.-
Adenosine
K72T3FS567
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1008305Subventions
Organisme : NIAID NIH HHS
ID : T32 AI007647
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007381
Pays : United States
Organisme : NIAID NIH HHS
ID : F31 AI145557
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI125236
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI120998
Pays : United States
Organisme : NIAID NIH HHS
ID : R56 AI141343
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM113194
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM113886
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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