Genetic Variability of Long Terminal Repeat Region between HIV-2 Groups Impacts Transcriptional Activity.
Binding Sites
Female
France
/ epidemiology
Gene Deletion
Gene Expression Regulation, Viral
Genetic Variation
HEK293 Cells
HIV Infections
/ virology
HIV Long Terminal Repeat
/ genetics
HIV-2
/ genetics
Humans
Leukocytes, Mononuclear
/ virology
Male
Middle Aged
Mutation
Phylogeny
Proviruses
/ genetics
Transcription, Genetic
tat Gene Products, Human Immunodeficiency Virus
/ genetics
ETS transcription factors
human immunodeficiency virus
long terminal repeat
transcription factors
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
17 03 2020
17 03 2020
Historique:
received:
01
09
2019
accepted:
13
12
2019
pubmed:
10
1
2020
medline:
15
9
2020
entrez:
10
1
2020
Statut:
epublish
Résumé
The HIV-2 long terminal repeat (LTR) region contains several transcription factor (TF) binding sites. Efficient LTR transactivation by cellular TF and viral proteins is crucial for HIV-2 reactivation and viral production. Proviral LTRs from 66 antiretroviral-naive HIV-2-infected patients included in the French ANRS HIV-2 CO5 Cohort were sequenced. High genetic variability within the HIV-2 LTR was observed, notably in the U3 subregion, the subregion encompassing most known TF binding sites. Genetic variability was significantly higher in HIV-2 group B than in group A viruses. Notably, all group B viruses lacked the peri-ETS binding site, and 4 group B sequences (11%) also presented a complete deletion of the first Sp1 binding site. The lack of a peri-ETS binding site was responsible for lower transcriptional activity in activated T lymphocytes, while deletion of the first Sp1 binding site lowered basal or Tat-mediated transcriptional activities, depending on the cell line. Interestingly, the HIV-2 cellular reservoir was less frequently quantifiable in patients infected by group B viruses and, when quantifiable, the reservoirs were significantly smaller than in patients infected by group A viruses. Our findings suggest that mutations observed
Identifiants
pubmed: 31915276
pii: JVI.01504-19
doi: 10.1128/JVI.01504-19
pmc: PMC7081896
pii:
doi:
Substances chimiques
tat Gene Products, Human Immunodeficiency Virus
0
Types de publication
Comparative Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2020 American Society for Microbiology.
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