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Distinctive variation in the U3R region of the 5' Long Terminal Repeat from diverse HIV-1 strains.
Abstract
Functional mapping of the 5'LTR has shown that the U3 and the R regions (U3R) contain
a cluster of regulatory elements involved in the control of HIV-1 transcription and
expression. As the HIV-1 genome is characterized by extensive variability, here we
aimed to describe mutations in the U3R from various HIV-1 clades and CRFs in order
to highlight strain specific differences that may impact the biological properties
of diverse HIV-1 strains. To achieve our purpose, the U3R sequence of plasma derived
virus belonging to different clades (A1, B, C, D, F2) and recombinants (CRF02_AG,
CRF01_AE and CRF22_01A1) was obtained using Illumina technology. Overall, the R region
was very well conserved among and across different strains, while in the U3 region
the average inter-strains nucleotide dissimilarity was up to 25%. The TAR hairpin
displayed a strain-distinctive cluster of mutations affecting the bulge and the loop,
but mostly the stem. Like in previous studies we found a TATAA motif in U3 promoter
region from the majority of HIV-1 strains and a TAAAA motif in CRF01_AE; but also
in LTRs from CRF22_01A1 isolates. Although LTRs from CRF22_01A1 specimens were assigned
CRF01_AE, they contained two NF-kB sites instead of the single TFBS described in CRF01_AE.
Also, as previously describe in clade C isolates, we found no C/EBP binding site directly
upstream of the enhancer region in CRF22_01A1 specimens. In our study, one-third of
CRF02_AG LTRs displayed three NF-kB sites which have been mainly described in clade
C isolates. Overall, the number, location and binding patterns of potential regulatory
elements found along the U3R might be specific to some HIV-1 strains such as clade
F2, CRF02_AG, CRF01_AE and CRF22_01A1. These features may be worth consideration as
they may be involved in distinctive regulation of HIV-1 transcription and replication
by different and diverse infecting strains.
Type
Journal articleSubject
HumansHIV-1
HIV Infections
Evolution, Molecular
Transcription, Genetic
Gene Expression Regulation, Viral
Recombination, Genetic
HIV Long Terminal Repeat
Genome, Viral
Genetic Variation
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https://hdl.handle.net/10161/17799Published Version (Please cite this version)
10.1371/journal.pone.0195661Publication Info
Mbondji-Wonje, Christelle; Dong, Ming; Wang, Xue; Zhao, Jiangqin; Ragupathy, Viswanath;
Sanchez, Ana M; ... Hewlett, Indira (2018). Distinctive variation in the U3R region of the 5' Long Terminal Repeat from diverse
HIV-1 strains. PloS one, 13(4). pp. e0195661. 10.1371/journal.pone.0195661. Retrieved from https://hdl.handle.net/10161/17799.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Thomas Norton Denny
Professor in Medicine
Thomas N. Denny, MSc, M.Phil, is the Chief Operating Officer of the Duke Human Vaccine
Institute (DHVI), Associate Dean for Duke Research and Discovery @RTP, and a Professor
of Medicine in the Department of Medicine at Duke University Medical Center. He is
also an Affiliate Member of the Duke Global Health Institute. Previously, he served
on the Health Sector Advisory Council of the Duke University Fuquay School of Business.
Prior to joining Duke, he was an Associate Professor of Pathology, Labo

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