PMID- 27633452
OWN - NLM
STAT- MEDLINE
DCOM- 20171116
LR  - 20231213
IS  - 1872-9096 (Electronic)
IS  - 0166-3542 (Linking)
VI  - 134
DP  - 2016 Oct
TI  - Targeting deoxyhypusine hydroxylase activity impairs cap-independent translation 
      initiation driven by the 5'untranslated region of the HIV-1, HTLV-1, and MMTV 
      mRNAs.
PG  - 192-206
LID - S0166-3542(16)30239-X [pii]
LID - 10.1016/j.antiviral.2016.09.006 [doi]
AB  - Replication of the human immunodeficiency virus type 1 (HIV-1) is dependent on 
      eIF5A hypusination. Hypusine is formed post-translationally on the eIF5A 
      precursor by two consecutive enzymatic steps; a reversible reaction involving the 
      enzyme deoxyhypusine synthase (DHS) and an irreversible step involving the enzyme 
      deoxyhypusine hydroxylase (DOHH). In this study we explored the effect of 
      inhibiting DOHH activity and therefore eIF5A hypusination, on HIV-1 gene 
      expression. Results show that the expression of proteins from an HIV-1 molecular 
      clone is reduced when DOHH activity is inhibited by Deferiprone (DFP) or 
      Ciclopirox (CPX). Next we evaluated the requirement of DOHH activity for internal 
      ribosome entry site (IRES)-mediated translation initiation driven by the 
      5'untranslated region (5'UTR) of the full length HIV-1 mRNA. Results show that 
      HIV-1 IRES activity relies on DOHH protein concentration and enzymatic activity. 
      Similar results were obtained for IRES-dependent translation initiation mediated 
      by 5'UTR of the human T-cell lymphotropic virus type 1 (HTLV-1) and the mouse 
      mammary tumor virus (MMTV) mRNAs. Interestingly, activity of the poliovirus IRES, 
      was less sensitive to the targeting of DOHH suggesting that not all viral IRESs 
      are equally dependent on the cellular concentration or the activity of DOHH. In 
      summary we present evidence indicating that the cellular concentration of DOHH 
      and its enzymatic activity play a role in HIV-1, HTLV-1 and MMTV IRES-mediated 
      translation initiation.
CI  - Copyright (c) 2016 Elsevier B.V. All rights reserved.
FAU - Caceres, C Joaquin
AU  - Caceres CJ
AD  - Laboratorio de Virologia Molecular, Instituto Milenio de Inmunologia e 
      Inmunoterapia, Departamento de Enfermedades Infecciosas e Inmunologia Pediatrica, 
      Escuela de Medicina, Pontificia Universidad Catolica de Chile, Marcoleta 391, 
      Santiago, Chile.
FAU - Angulo, Jenniffer
AU  - Angulo J
AD  - Laboratorio de Virologia Molecular, Instituto Milenio de Inmunologia e 
      Inmunoterapia, Departamento de Enfermedades Infecciosas e Inmunologia Pediatrica, 
      Escuela de Medicina, Pontificia Universidad Catolica de Chile, Marcoleta 391, 
      Santiago, Chile.
FAU - Contreras, Nataly
AU  - Contreras N
AD  - Laboratorio de Virologia Molecular, Instituto Milenio de Inmunologia e 
      Inmunoterapia, Departamento de Enfermedades Infecciosas e Inmunologia Pediatrica, 
      Escuela de Medicina, Pontificia Universidad Catolica de Chile, Marcoleta 391, 
      Santiago, Chile.
FAU - Pino, Karla
AU  - Pino K
AD  - Laboratorio de Virologia Molecular, Instituto Milenio de Inmunologia e 
      Inmunoterapia, Departamento de Enfermedades Infecciosas e Inmunologia Pediatrica, 
      Escuela de Medicina, Pontificia Universidad Catolica de Chile, Marcoleta 391, 
      Santiago, Chile.
FAU - Vera-Otarola, Jorge
AU  - Vera-Otarola J
AD  - Laboratorio de Virologia Molecular, Instituto Milenio de Inmunologia e 
      Inmunoterapia, Departamento de Enfermedades Infecciosas e Inmunologia Pediatrica, 
      Escuela de Medicina, Pontificia Universidad Catolica de Chile, Marcoleta 391, 
      Santiago, Chile.
FAU - Lopez-Lastra, Marcelo
AU  - Lopez-Lastra M
AD  - Laboratorio de Virologia Molecular, Instituto Milenio de Inmunologia e 
      Inmunoterapia, Departamento de Enfermedades Infecciosas e Inmunologia Pediatrica, 
      Escuela de Medicina, Pontificia Universidad Catolica de Chile, Marcoleta 391, 
      Santiago, Chile. Electronic address: malopez@med.puc.cl.
LA  - eng
PT  - Journal Article
DEP - 20160912
PL  - Netherlands
TA  - Antiviral Res
JT  - Antiviral research
JID - 8109699
RN  - 0 (5' Untranslated Regions)
RN  - 0 (Peptide Initiation Factors)
RN  - 0 (Pyridones)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA-Binding Proteins)
RN  - 19W019ZDRJ (Ciclopirox)
RN  - 2BTY8KH53L (Deferiprone)
RN  - EC 1.- (Mixed Function Oxygenases)
RN  - EC 1.14.99.29 (deoxyhypusine hydroxylase)
SB  - IM
MH  - *5' Untranslated Regions
MH  - Animals
MH  - Ciclopirox
MH  - Deferiprone
MH  - Gene Expression
MH  - HEK293 Cells
MH  - HIV-1/drug effects/*genetics/*physiology
MH  - HeLa Cells
MH  - Human T-lymphotropic virus 1/*genetics
MH  - Humans
MH  - Mammary Tumor Virus, Mouse/drug effects/*genetics
MH  - Mice
MH  - Mixed Function Oxygenases/*antagonists & inhibitors/drug effects
MH  - Peptide Initiation Factors/drug effects
MH  - Protein Biosynthesis/drug effects
MH  - Pyridones/pharmacology
MH  - RNA, Messenger/drug effects
MH  - RNA-Binding Proteins/drug effects
MH  - Eukaryotic Translation Initiation Factor 5A
OTO - NOTNLM
OT  - DOHH
OT  - HIV-1
OT  - HTLV-1 MMTV
OT  - IRES
OT  - Protein synthesis
OT  - RNA
OT  - eIF5A
EDAT- 2016/09/17 06:00
MHDA- 2017/11/29 06:00
CRDT- 2016/09/17 06:00
PHST- 2016/04/21 00:00 [received]
PHST- 2016/09/12 00:00 [accepted]
PHST- 2016/09/17 06:00 [pubmed]
PHST- 2017/11/29 06:00 [medline]
PHST- 2016/09/17 06:00 [entrez]
AID - S0166-3542(16)30239-X [pii]
AID - 10.1016/j.antiviral.2016.09.006 [doi]
PST - ppublish
SO  - Antiviral Res. 2016 Oct;134:192-206. doi: 10.1016/j.antiviral.2016.09.006. Epub 
      2016 Sep 12.